3 Biotech (2023) 13:1

https://doi.org/10.1007/s13205-022-03398-7

REVIEW ARTICLE

Antibacterial potential of chalcones and its derivatives

against Staphylococcus aureus
Larissa da Silva1 · Isydorio Alves Donato1 · Cicera Alane Coelho Gonçalves1 · Jackelyne Roberta Scherf2 ·
Hélcio Silva dos Santos3 · Edna Mori4 · Henrique Douglas Melo Coutinho5 · Francisco Assis Bezerra da Cunha1

Received: 9 August 2022 / Accepted: 12 October 2022 / Published online: 1 December 2022
© King Abdulaziz City for Science and Technology 2022

Abstract
Chalcones are natural substances found in the metabolism of several botanical families. Their structure consists of 1,3-diphe-
nyl-2-propen-1-one and they are characterized by having in their chains an α, β-unsaturated carbonyl system, two phenol
rings and a three-carbon chain that unites them. In plants, Chalcones are mainly involved in the biosynthesis of flavonoids
and isoflavonoids through the phenylalanine derivation. This group of substances has been shown to be a viable alternative
for the investigation of its antibacterial potential, considering the numerous biological activities reported and the increase of
the microbial resistance that concern global health agencies. Staphylococcus aureus is a bacterium that has stood out for its
ability to adapt and develop resistance to a wide variety of drugs. This literature review aimed to highlight recent advances
in the use of Chalcones and derivatives as antibacterial agents against S. aureus, focusing on research articles available on
the Science Direct, Pub Med and Scopus data platforms in the period 2015–2021. It was constructed informative tables that
provided an overview of which types of Chalcones are being studied more (Natural or Synthetic); its chemical name and
main Synthesis Methodology. From the analysis of the data, it was observed that the compounds based on Chalcones have
great potential in medicinal chemistry as antibacterial agents and that the molecular skeletons of these compounds as well
as their derivatives can be easily obtained through substitutions in the A and B rings of Chalcones, in order to obtain the
desired bioactivity. It was verified that Chalcones and derivatives are promising agents for combating the multidrug resist-
ance of S. aureus to drugs.

Keywords Bioactivity · Multi-resistance · Efflux pump · Structure–activity relationship

Introduction

The emergence and availability of antibiotics have revolu-

tionized the treatment of diseases in the 20th century, but
this achievement is threatened due to the development of
* Henrique Douglas Melo Coutinho resistance of microorganisms, which reduces the effective-
[email protected]
ness of several classes of antibiotics for clinical use (Dan and
1
Laboratory of Semi‑Arid Bioprospecting (LABSEMA), Dai 2019). There are several factors by which microorgan-
Department of Biological Chemistry, URCA​, Crato, CE, isms acquire or develop resistance to a drug, the most pre-
Brazil dominant among them is through a process known as natural
2
Graduate Program in Pharmaceutical Sciences, Federal selection, in which the most sensitive microorganisms to
University of Pernambuco, UFPE, Recife, PE, Brazil the drug are eliminated and those that manage to survive
3
Laboratory of Chemistry of Natural and Synthetic Product, the action of the antimicrobial develop resistance (Loureiro
State university of Ceará, UECE, Fortaleza, CE, Brazil et al. 2016). Bacterial resistance has become a subject of
4
CECAPE, College of Dentistry, Juazeiro do Norte, global concern, and for this reason, more and more research-
CE 63024‑015, Brazil ers around the world are engaged in the search for natural
5
Laboratory of Microbiology and Molecular Biology or synthetic products with antibacterial potential (Oliveira
(LMBM), Department of Biological Chemistry, URCA​, et al. 2020; Rezende-Junior et al. 2020).
Crato, CE, Brazil

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It is estimated that approximately 700,000 deaths are Chemically, Chalcones are known as α, β-unsaturated
caused by infections of drug-resistant bacteria per year and ketones with a structure consisting in 1,3-diphenyl-2-pro-
this number could reach 10 million deaths per year by 2050 pen-1-one and are the main precursors of Flavonoids and
if urgent measures are not taken, according to the report of Isoflavonoids (Fig. 1) (Ferreira et al. 2018). This group of
Neill (2016). In this perspective, the microorganism that has substances has drawn attention for presenting several bio-
most concerned global health bodies is the gram-positive logical activities of clinical interest, such as antitumor, anti-
bacterium Staphylococcus aureus. This pathogenic bacte- inflammatory, anti-oxidant and antimicrobial activities,
rium belongs to the group of Coccus and is responsible for which demonstrates the importance of these compounds
several diseases that affect humans. It is currently one of the (Rashid et al. 2019; Matos et al. 2015).
pathogens of greatest clinical interest due to its high ability It is important to emphasize that Chalcones are con-
to colonize and acquire resistance to multiple drugs (Mul- sidered important scaffolds for the synthesis of new drugs
tiple Drug Resistance—MDR) (Grace and Fetsch 2017). through the manipulation of their aromatic rings, which
Sophisticated resistance mechanisms were developed and can potentiate already proven biological activities or lead
acquired by this species after years of exposure to antibacte- to the discovery of new bioactivities, including antibacte-
rials (Guo et al. 2020). Enzyme synthesis; Reduction in the rial activity (Bitencourt et al. 2019). These compounds are
absorption of endogenous molecules; Molecular modifica- currently being explored with published studies about syn-
tion of the target; Acquisition of genetic material through thesis, molecular targets and biological activities (Dan and
mobile genetic elements, such as plasmids; and efflux pumps Dai 2019). Within this context, the present review aims to
are examples of resistance mechanisms present in S. aureus highlight recent advances in the use of natural and synthetic
(Abushaheen et al. 2020). Chalcones as well as their derivatives used as antibacterial
Natural compounds are considered a good alternative for agents against S. aureus, focusing on research articles pub-
the development of new antibiotics because they are prod- lished in the period of 2015–2021.
ucts of natural selection, shaped by evolution to interact with
cellular targets with high efficiency and selectivity, in addi-
tion to presenting important properties that allows interac- Methodology
tion with different bacterial cellular targets, preventing cell
survival after contact with the antimicrobial (Wright 2017; This literature review was carried out by consulting scien-
Rossiter et al. 2017). tific articles available in different databases. All stages of
Human civilization has long used natural products as the collection, screening and analysis of the articles selected for
main source of products with therapeutic potential. Cur- this review meet a guiding question that follows systematic
rently, more than half of clinical drugs come from natural methods. The research started in October 2021 and ended in
products and their synthetic derivatives, according to the January 2022. To achieve the research proposal, the follow-
United States Food and Drug Administration (FDA), which ing methodological procedures were applied.
analyzed in detail the introduction of new drugs in the clinic
until 2014 (Dan and Dai 2019; Newman and Cragg 2016). Database
In this sense, Chalcones have gained prominence in
medicinal chemistry due to their important pharmacologi- The data platforms used for the collection of material that
cal properties. Chalcones are natural substances present led to the realization of this review were: (1) Science Direct
in the secondary metabolism of several botanical species, (https://​www.​scien​cedir​ect.​com); (2) Pub Med (https://​
including the so-called medicinal plants. Medicinal plants pubmed. ​ n cbi. ​ n lm. ​ n ih. ​ g ov/); (3) Scopus (https://​ w ww-​
are considered by the WHO as any plant that presents in perio​dicos-​capes-​gov-​br.​ezl.​perio​dicos.​capes.​gov.​br). The
its metabolism compounds with some therapeutic potential
(Who 2021). In this sense, several botanical species that
have chalcones in their composition and present therapeutic
effects of clinical interest are reported in the literature (Fer-
reira et al. 2018). The Ficus microcarpa species presents a
high content of chalcones in its roots and has already had
its medicinal and antibacterial properties investigated and
proven (Díaz-Tielas 2016; Kalaskar and Surana 2012). They
can also be found in the leaves and fruits of species of the
genus Artocarpus that is widely used for the treatment or
prevention of inflammation, malaria, and vitiligo, mainly in
tropical Asian regions (Pereira and Kaplan 2013). Fig. 1  Fundamental structure of chalcones. Source: Author (2022)

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research was carried out with the application of specific were organized in Microsoft Word software. Finally, a
descriptors and filters. descriptive analysis of the bibliographic sample was carried
out, accompanied by a discussion on the aspects addressed
Descriptors and filters used by the included studies.

Wide-descriptors were selected in order to compile the

largest number of studies and avoid missing out on relevant Results and discussion
research to be included. Thus, the descriptors: “Chalconas
AND Staphylococcus aureus” were inserted in a combined The content of the articles researched allowed us to evaluate
way in the databases cited above. To better meet the origi- recent developments in scientific research involving the use
nality of studies on antibacterial activity of Chalcones on of natural and synthetic Chalcones and their derivatives in
S. aureus, were used filters such as: Type of article, Year of the fight against infections caused by S. aureus. The data
publication and Language. obtained from the three search platforms resulted in 697
articles using the descriptors and filters as a basis for the
Eligibility criteria research (general prospection). With the application of pre-
established eligibility criteria, this step being considered as
In terms of data mining and the established eligibility crite- the first screening, this number was reduced to 188 viable
ria, the following inclusion criteria were defined: Original articles for analysis.
research articles focusing on the investigation of the antibac- The second screening was carried out by reading the arti-
terial potential of Chalcones of natural and synthetic origin cles selected in the first screening and including those that
and their derivatives on S. aureus bacteria; in vitro studies; met the proposal of this review, excluding duplicate arti-
English, Portuguese and Spanish Language; Studies pub- cles within the same platform. The third and last step was
lished in the period 2015–2021. The exclusion criteria were: the analysis and exclusion of duplicates between platforms.
Course Completion Works; Dissertations; Theses; Annals Table 1 shows in detail the number of articles obtained at
of events; Case reports; in silico and in vivo studies; Book; each stage of collection.
Bibliographic reviews; Duplicates; Incomplete works, with The PRISMA flowchart was assembled to demonstrate
unavailable access or that do not fit the proposed theme. the process of metabolizing the results that includes the pro-
cesses of inclusion and exclusion of articles for each step of
Analytical approach the search until reaching the final number of studies consid-
ered for this study (Fig. 2).
The articles found went through three stages of screening In Tables 2 and 3 below, containing all the articles ana-
in order to select those that fit the proposal of this review. lyzed and selected to compose the present review, it is possi-
The first step was defined as general prospecting, where all ble to observe that 84.83% of the collected studies report the
articles found on each platform were analyzed based on the work with synthetic Chalcones to evaluate the antibacterial
descriptors and filters used. The three screening processes activity against S. aureus while the natural Chalcones repre-
were based on reading all filtered articles as well as eliminat- sent 15.17% of the works. This demonstrates the interest of
ing duplicates found on the same platform and among the research in the investigation of new compounds from natural
three databases. substances in order to potentiate known bioactivities or dis-
After analyzing the articles, the analytical approach used cover new activities, whether in reversing bacterial resist-
consisted of producing informative tables containing the ance or reinforcing the antibiotic effect of existing drugs.
selected articles with the following information: Chemical The present review was based on studies on the bacte-
name of the Chalcone used; Chalcone type (natural or syn- rium S. aureus, justified by the importance of this micro-
thetic); Synthesis method; Bacterial Strain, MIC/Inhibition organism as it is currently considered one of the main
Zone, Activity and Representative Reference. Tabulations bacteria of clinical and epidemiological importance. This

Table 1  Number of articles Database General prospec- First screening Second screen- Exclusion of duplicates
prospected on each platform tion ing
visited and the screening
processes Science direct 320 33 30 18 common articles
Pub Med 100 58 48 among the three
platforms
Scopus 277 97 85
Sum 697 188 163 145

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1 Page 4 of 30 3 Biotech (2023) 13:1

Fig. 2  - PRISMA flowchart of

the analytical steps for building
the review. Source: Author

Identification
(2022) Number of articles identified in the
databases*:
(n = 697)

Excluded after applying

filters and eligibility
criteria
(n = 509)
Screening

Excluded for not

Articles selected for the
meeting the review
first screening
proposal
(n = 188)
(n = 25)

Articles selected for the Exclusion of duplicates

second screening between the three
(n = 163) platforms
(n = 18)
Included

Studies included in review

(n = 145)

importance is due to its high ability to persist as a com- best known strains today, the MRSA (Methicillin-Resistant
mensal microorganism in addition to its frequent multi- Staphylococcus aureus) (Kalenić 2012; Mendes 2010).
resistance to antimicrobials and its various virulence fac- The tables also show different types of S. aureus strains,
tors, expressing a countless variety of proteins, toxins and especially MRSA and MSSA (Methicillin-Sensitive Staphy-
polysaccharides at the extracellular level (Barroso et al. lococcus aureus), which are considered the second leading
2014). It is assumed that 80% of the world population is cause of longer hospitalizations, increasing human mortality
intermittently colonized by this bacterium, acting as the and morbidity rates, resulting in a economic and political
main successful pathogen at hospital and community level, weight worldwide (Mendes 2010; Purrello et al. 2014).
being mainly involved in pyogenic and toxic infections The main methods of synthesis of Chalcones and its
(Silva 2016). derivatives were also observed. Recently, derivation of prod-
The sequencing of genomes from different strains of ucts from Chalcones has been the subject of investigations
S. aureus led to the discovery of a high number of mobile due to its relatively simple structure and the variety of bio-
genetic elements, which explains the dissemination of logical activities that they present (Ferreira et al. 2018). The
increasingly resistant strains, since horizontal gene transfer set of activities expressed is in part attributed to the immense
is the main cause of multidrug resistance in bacteria (Assef possibilities of substitutions in the aromatic rings of Chal-
and Neto 2020). This line of reasoning can be justified by cones, since the Claisen–Schmidt methodology, which is one
the first case of S. aureus resistance to Methicillin that was of the main methodologies used for the synthesis of these
identified in the United Kingdom 1 year after the introduc- compounds, promotes the obtainment of a large amount of
tion of this antibiotic in the clinic, resulting in one of the compounds, due to the existence of numerous commercial

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 Table 2  Synthesis matrix of articles collected in a literature review that report the antibacterial potential of natural Chalcones against S. aureus
Chalcone Type S. aureus strain(s) MIC/Inhibition Zone Activity Quotes

4′-Hydroxy-3–4-dimethoxy- Nature ATCC 25,923; IS-58; RN-4220; 1024; ≥ 1024 μg/mL Inactive for antibacterial activ- Rezende-JúNIOR et al. (2020)
chalcone (1); Isolated from Arrabidaea SA1199-B; K2068; K4414; ity
3′-Hydroxy-3-acetate, 4-meth- brachypoda K4100
3 Biotech (2023) 13:1

oxy-chalcone (3);
3′,4′-dihydroxy, 3,4,4′-trimeth-
oxy-chalcone (4);
3,4-dimethoxy-chalcone (5)
3′,4′-dihydroxy, 3,4,4′-trimeth- Nature SA1199-B 16 µg / mL NorA efflux pump inhibitor Rezende-JúNIOR et al. (2020)
oxy-chalcone (4) Isolated from Arrabidaea 4X
brachypoda
Lophirones B, C Nature, isolated from Lophira ATCC 29,213 150 – 200 µg/ml Antibacterial Ajiboye and Haliru (2016)
alata
4,4′,6′ trihydroxy 3 methoxy 3′ Nature, isolated from Ela- ATCC 6538 7.8 μg/ml Antibacterial Mariani et al. (2016)
pentene chalcone tostema parasiticum
Grandiflorone Nature, isolated from Lepto- - 16–32 μg/ml Antibacterial Killeen et al. (2016)
spermum scoparium
2ʹ,4ʹ-dihydroxychalcone Nature ATCC 29,213, MRSA, MRSCN 250 µg/mL−1 Antibacterial Moreno et al. (2015)
e 2ʹ,4ʹ-dihydroxy-3ʹ- Isolated from Zuccagnia punc-
methoxychalcone tata Cav
Cinnamaldehydo and its Chal- Nature MRSA 3.21 ± 40.0 mm Antibacterial Khayyat and Saddiq (2015)
cones derivatives Isolated from Cinnamomum
verum
2′,4′-dihydroxychalcone Nature ATCC 6538 31 μg/mL Antibacterial Joray et al. (2015)
7-hydroxyflavanone Isolated from Flourensia 62 μg/mL
oolepis
Xanthoangelol Nature, isolated from Angelica ATCC 25,923, ATCC 700,699 6,25 µM Antibacterial Meier et al. (2019)
keiskei (MRSA) 3,12 µM
Isobavachalcone; Nature, isolated from Psoralea MRSA OM481 OM584 8—16 µg/mL Antibacterial Cui et al. (2015)
corylifol B corylifolia L
20 -hydroxy-4,40,60 -tri- Nature, isolated from hispidum ATCC 25,923 62,5 mg/mL—125 µg/ml Antibacterial and anti-biofilm Costa et al. (2013)
methoxychalcone, 20
-hydroxy-4,40,60 -tetrameth-
oxychalcone, and 3,20
-dihydroxy-4,40,60 -trimeth-
oxychalcone
Prenylated Chalcones (xantho- Nature, isolated from Humulus 8146, 8147, CIP 224, T1.1, 9,8 – 19,5 µg/ml Antibacterial, synergism with Bocquet et al. (2019)
humol and Desmethylxantho- lupulus L T25.10, T25.3, T25.9, T26A4, gentamicin, amoxicillin and
humol) T28.1, T36B1, T47A12, T6.7 vancomycin and anti-biofilm
Lophirones B, C Nature, isolated from Bamburu ATCC 29,213 Redução da MIC Antibacterial Ajiboye and Haliru (2016)
village
Calythropsin Nature, isolated from Calico- - 18 ± 1.4 mm Antibacterial Alhage et al. (2018)
tome villosa 6 ± 0.7 mm

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Table 2  (continued)
Chalcone Type S. aureus strain(s) MIC/Inhibition Zone Activity Quotes

Diuvaretin, Uvaretin and Iso- Nature, isolated from Uvaria ATCC 25,923, 0,0046 mg/mL Antibacterial Koudokpon et al. (2018)
Page 6 of 30

Uvaretin chamae
Basalcone J Nature, isolated from Populus ATCC 25,923 0.61 μM Antibacterial Simard et al. (2015)
Balsamifera 6 μM
20 -hydroxy-4,40 -dimethoxy- Nature, isolated from Coreopsis - Redução de MIC Antibacterial Begmatov et al. (2020)

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chalcone and isoliquiritigenin tinctoria Nutt
5′-O-Methyl-3-hydroxyflem- Nature, isolated from Desmo- ATCC 43,300, 32 μg/mL Antibacterial Rees et al. (2015)
ingin A and 5′-O-Methylflem- dium congestum NRSA-NRS 17, NRSA-NRS 1
ingin C
Isosalipurposide Nature, isolated from Corylop- 693E, 1.23 ± 0.06 cm Antibacterial Seo et al. (2016)
sis coreana MRSA 693E
Homoembelin Nature ATCC 1026, SA3, SA4, SA11, ≥ 256 µg/mL Inactive for antibacterial activ- Omosa et al. (2016)
SA12, MRSA 3, MRSA 4, ity
MRSA 6, MRSA 8
Xanthoangelol Nature ATCC 700,699 (MRSA) 3.125 µM Antibacterial Meier et al. (2019)
Derived from Amorpha fruc- 12,5 µM Bactericidal
ticosa
2', 4'-dihydroxychalcone Nature (F2, F5, F7, F8, F22, F23) and (25 µg/mL) Antibacterial Nuño et al. (2018)
*
(DHC) Isolated from F31 100 µg/mL
Zuccagnia punctata Cav
2', 4'-dihydroxy-3'-methoxy- Nature (F2, F5, F7, F8, F22, F23) and (25 µg/mL) Antibacterial Nuño et al. (2018)
*
calcone Isolated from F31 100 µg/mL
(DMHC) Zuccagnia punctata Cav
2', 4'-dihydroxychalcone Nature F7 12,5 µg/mL Anti-biofilm Nuño et al. (2018))
(DHC) Isolated from ATCC 25,923
Zuccagnia punctata Cav
Isoliquiritigenin Nature ATCC 29,223 62,5 µg/mL Low antibacterial activity Cuellar et al. (2020)
Isolated from
Platymiscium gracile Benth

a) The spaces filled with (-) mean that the information was absent from the article or was not clear
3 Biotech (2023) 13:1
 Table 3  Synthesis matrix of articles collected in a literature review that report the antibacterial potential of synthetic Chalcones and derivatives against S. aureus
Chalcone Type Synthesis technique S. aureus strain (s) MIC/Inhibition Zone Activity Quote

(E)-1-(2-hydroxyphenyl)- Synthetic – 1199B ↓ 50% of the MIC of the Antibacterial; Synergism Rocha et al. (2021)
3-(2,4-dimethoxy-3-meth- antibiotic with the antibiotic
ylphenyl)prop-2-en-1-one (128 μg/mL to 64 μg/ Norfloxacin
3 Biotech (2023) 13:1

mL); Inactive as a NorA

inhibitor
(E)-1-(2-hydroxyphenyl)- Synthetic – K2068 ↓ 60.3% of the MIC of Inactive for direct Rocha et al. (2021)
3-(2,4-dimethoxy-3-meth- BrEt (32 μg/mL to antibacterial activity.
ylphenyl)prop-2-en-1-one 12.6992 μg/mL) Synergism with BrEt
and potential MepA
efflux pump inhibitor
(Z)-4-((bis(2-hydroxyethyl) Synthetic – MRSA 0.004 mM Antibacterial Hu et al. (2021)
amino)methyl)-7-((1- 6X better than the
(4-methoxyphenyl)- reference antibiotic
3-oxo-3-(thiazol-2-yl) Norfloxacin
prop-1-en-2-yl) oxy)-2H-
chromen-2-one (5i)
4-bromo-3'-aminochalcone Synthetic Claisen–Schmidt MSSA 1.9 μg mL; Concentration-depend- Garcia et al. (2021)
(5f) MRSA 7.8 µg mL ent antibacterial and
antibiofilm
Chalcones derived from Synthetic Claisen–Schmidt RN4220; K4414; 1199B; 1024 μg/mL Clinically irrelevant Xavier et al. (2021)
2-hydroxyacetophenone K2068 antibacterial activity;
(A1-A6) Potential IBEs
Chalcone derivative Synthetic Claisen–Schmidt – Over than 15 mm Bactericide Shinde et al. (2021)
DBDCPP-3
(E)-3-(furan-2-yl)-1-(2- Synthetic Claisen–Schmidt 1199B 1024 μg/mL Clinically irrelevant da Silva et al. (2021)
hydroxy-3,4,6-trimethoxy- K2068 antibacterial activity;
phenyl)prop 2-en-1-one Potential NorA and
(Hitfurfural); MepA IBEs
(E)-1-(2-hydroxy-3,4-
dimethoxyphenyl)-3-
(thiophen-2-yl)prop-2-en-
1-one (Hithiophene)
(2E)-3-(4-Methoxyphenyl)- Synthetic – – 3.12 μM Antibacterial Ibrahim et al. (2021)
1-{4-[(3-phenyl-1,2,4- 2 × more efficient than
oxadiazol-5- yl)methoxy] the standard drug
phenyl}prop-2-en-1-one Ciprofloxacin
(6a)
(E)-3-(3-bromo-4- Synthetic Claisen–Schmidt MTCC 916 18 mm Antibacterial Johnson and Yardily
methoxyphenyl)-1-(thiazol- (2021)
2-yl)prop-2-en-1-one
(Zn 4 complex)

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Page 7 of 30 1
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Table 3  (continued)
Chalcone Type Synthesis technique S. aureus strain (s) MIC/Inhibition Zone Activity Quote

(E)-3-(4-(dimethylamino) Synthetic Claisen–Schmidt 1199B 1000 μg/mL Clinically irrelevant Leal et al. (2021)
Page 8 of 30

phenyl)-1-(2-hydroxyphe- antibacterial activ-

nyl)prop-2-en1-one (3) ity; NorA inhibitory
potential
Polymer chalcone (P3) Synthetic Claisen–Schmidt – 20 mm Antibacterial Solmaz et al. (2021)

13
Hybrid Chalcona (1) Synthetic Claisen–Schmidt NCIM 2122 10.05 μM Low antibacterial activ- Konidala et al. (2021)
ity compared to stand-
ard drug Ciprofloxacin
Chalcone with imide-Zo Synthetic Claisen–Schmidt – 32 μg/mL and 64 μg/mL Antibacterial Soltani et al. (2021)
portion [1,2-a]pyridine (3b,
3d, 3g, 3l and 3m)
E4,4'-Bromo-4-methylchal- Synthetic Claisen–Schmidt MRSA 16 μg/mL Antibacterial Aksöz et al. (2021)
cone
Quinoline chalcone: Synthetic Claisen–Schmidt – At a concentration of Low antibacterial Saleh et al. (2020)
1-(4-(benzyl sulfonyl) 10 mg/disk: activity compared to
phenyl)- 2,3dibromo-3- 15 mm standard drug
(chloroquinoline-3-yl)
propane-1- one (7)
Fluorinated chalcone: Synthetic Claisen–Schmidt NCIM-2079 51 µM Low antibacterial Lagu et al. (2020)
(E)-3-(1″H-indol- activity compared to
3″-yl)-1-[40 -(trifluoro- standard drug
methyl)phenyl]prop-2-en-
1-one
(E)-1-(4-aminophenyl)-3- Synthetic Claisen–Schmidt 10 ≥ 1024 μg/mL Irrelevant Ferraz et al. (2020)
(furan-2-yl)-prop-2-en-1-
one (AFPO)
(E)-1-(4-aminophenyl)-3- Synthetic Claisen–Schmidt 10 AFPO + Gentamicin: Synergism (potentiation Ferraz et al. (2020)
(furan-2-yl)-prop-2-en-1- ↓ 3X of antibiotic activity)
one (AFPO) AFPO + Penicillin = ↓
3X
Naphthyl Chalcones (3a -3p) Synthetic – MTCC 96 24–162 μg/mL Low antibacterial Pola et al. (2020)
activity compared to
standard drug
Heteroaromatic Chalcones Synthetic Claisen–Schmidt N5923 13 and 19 mm Antibacterial Farooq and Ngaini (2020)
Derivatives (1a-and 3a-c)
Chalcone derivative (1d) Synthetic Claisen–Schmidt – 11 mm Antibacterial Farooq and Ngaini (2020)
Chalcones source of the Synthetic Claisen–Schmidt 10 (Multi-resistant); ≥ 1024 μg/mL; Irrelevant; Freitas et al. (2020)
natural product ATCC 25923; 645 μg/mL Low antibacterial activ-
2-hydroxy-3,4,6-trimethoxy- ity and synergism with
acetophenone (1–4) Ciprofloxacin and
Gentamicin
3 Biotech (2023) 13:1
 Table 3  (continued)
Chalcone Type Synthesis technique S. aureus strain (s) MIC/Inhibition Zone Activity Quote

4'-piperazinyl Chalcone— Synthetic Alcoholic condensation MRSA (ATCC 33591); 0.5–1 μg/mL Antibacterial Xie et al. (2020)
pleuromutilin MRSA (ATCC 43300);
(14i; 14k) ATCC 25923
3 Biotech (2023) 13:1

Sulfonamides Chalcones and Synthetic – ATCC 25923 (> 22)—10 (0.156) mm Inactive for antibacterial Bonakdar et al. (2020)
derivatives: (IV—XXXII) activity
Ferrocenyl Chalcones Synthetic Acquired NCIMB 8244 0.031 mg mL Antibacterial Henry et al. (2020)
(Decyl) MRSA (RCH) 0.063 mg mL
Bichalcones and Bispirazo- Synthetic Acquired – 16–32 μg/mL Inactive for antibacterial Nisa and Yusuf (2020)
line derivatives 8 – 32 μg/mL activity
(2ª–2d)
(3b–3d)
Pyrimidine derived from Synthetic Acquired ATCC 6538 7.81 μg/mL Antibacterial Sanad et al. (2020)
Chalcone:
9-(Benzo[d][1,3]dioxol-
5-yl)- 7-(thiophen-2-yl)
pyrido[30,20:4,5]
thieno[3,2-d]pyrimidin-
4(3H)-one (24a)
Triazine Chalcone: 3k Synthetic Claisen–Schmidt NCIM 2178 85 mm Antibacterial Shinde et al. (2019)
Aminochalcone derivatives: Synthetic Claisen–Schmidt DSM799 0.25 [mg/mL]; Antibacterial Kozłowska et al. (2019)
1–3; 7–8; 11–13; 16 0.125 [mg/mL];
0.25 [mg/mL];
0.5 [mg/mL]
Chalcones and derivatives Synthetic Claisen–Schmidt MSSA (ATCC 29213); (1.56 − 6.25 μg/mL); Antibacterial Zhang et al. (2018b)
(6r, 12a); MRSA (USA 300) [3.125 − 6.25 μg/mL];
[6s; 12c] 1.56 -12.5 μg/mL
7j–7m
Chalcones bonded to Biscou- Synthetic Polycondensation – 312.5 μg/mL; Antibacterial Kandaswamy (2019)
marine copolyester 625 μg/mL;
4a; 4b; 4c 156.2 μg/mL
1-(2-bromophenyl) ethanone Synthetic – NCIM 2079 They ranged from 31.25 Significant Antibacterial Prasad et al. (2018)
derivatives to 500 μg/mL
I1-I5
Chalcones derivatives Synthetic Claisen–Schmidt NTCC8325-4 50 and 70 µg/mL; Low antibacterial activ- Vásquez-Martínez et al.
11; 18 MRSA 97-7 50 and 90 µg/mL ity (2019)
Chalcones derivatives Synthetic Claisen–Schmidt MRSA 97-7 20 μg/mL; Synergism with the anti- Vásquez-Martínez et al.
18; 11 50 μg/mL biotic methicillin (2019)
Chalcone-pyridine hybrids Synthetic – MTCC 121 3.12 μg/mL; Antibacterial Gondru et al. (2018)
5j; 5i; 6.25 μg/mL
5b; 5f

13
Page 9 of 30 1
 1

Table 3  (continued)
Chalcone Type Synthesis technique S. aureus strain (s) MIC/Inhibition Zone Activity Quote

Pyrimidine-2(1H)-ol/-thiol Synthetic – ATCC 25923 2.1–138.8 µg/mL Antibacterial Fandakli et al. (2018)
derivatives derived from
Page 10 of 30

Chalcones
20–24; 35–39
Chalcones converted to Synthetic Claisen–Schmidt – They ranged from 3.75 Antibacterial Chowdary et al. (2019)

13
pyrazoles to 1.25 µg/mL
4h, 4j, 4l, 4m e 4n
Benzoxazepines derived Synthetic – – 30 mm; Antibacterial Ashok et al. (2018)
from pyrazol-Chalcones 28 mm;
3c; 3h, 5c, 5g; 27 mm;
5b; 5h 32 mm
Indolyl Chalcone Derivatives Synthetic – – 27 mm; Antibacterial Sayed et al. (2018)
4b; 5b; 6b, 7; 11 22 mm;
24 mm,
28 mm
Heterocyclic Chalcones Synthetic Claisen–Schmidt MTCC 096 12.5 µg/mL* Antibacterial Kaushik et al. (2018)
4b* 6.25 µg/mL
4c, 4g, 4k
Pyrazole Chalcones Synthetic Claisen–Schmidt MTCC9886 13 ± 0.44 mm; Moderate antibacterial Kumari et al. (2018)
6b; 6c; 7b e 8b 17 ± 1.10 mm;
15 ± 0.53 mm;
11 ± 2.01 mm
Triazole-based Chalcones Synthetic – – 44.59 mM; Antibacterial Santosh et al. (2018)
and its derivatives 50.15 mM;
3f, 5a, 6a, 7b e 8a 66.61 mM;
76.63 mM;
53.86 mM
Anthracene-based Chalcone Synthetic Claisen–Schmidt – 6.25 µg mL; Moderate antibacterial Prakash et al. (2018)
derivatives 3.12 µg mL
ANNP, ANFL;
ANID and ANPT
Chalcones derived from Synthetic – – – Antibacterial Santra et al. (2018)
acetylpyridines
4; 5; 11; 12
β-Carboline Chalcones and Synthetic – MTCC 96 Ranged from 440 Inactive for antibacterial Reddy et al. (2018)
their bromide salts to > 900 µM activity
12b, 12c, 12e, 12f, 12g; 13a;
13h
Chalcone-thiazole hybrids Synthetic Claisen–Schmidt ATCC 33592—Methicil- 1.4 µM Antibacterial Sashidhara et al. (2015)
(27) lin and Gentamicin
Resistant
3 Biotech (2023) 13:1
 Table 3  (continued)
Chalcone Type Synthesis technique S. aureus strain (s) MIC/Inhibition Zone Activity Quote

1,3- diphenyl-2-propen- Synthetic – JMC 2151 32 ± 1.5 mm Antibacterial Alam et al. (2015)
1-ones
(III-C)
3 Biotech (2023) 13:1

Chalcones derivatives: 3ª–3j Synthetic – ATCC 29213; (MRSA) 16–256 μg/mL Low antibacterial activ- Evranos-Aksöz et al.
32–64 μg/mL ity (2015)
4.5-dihydropyrazol Synthetic – ATCC 29213 10–17 mm Antibacterial Budak et al. (2017)
2-(4-Methyl-2-oxo-2H- Synthetic Claisen–Schmidt ATTC 6538 35.8 µg/mL Antibacterial El-Sherief et al. (2017)
chromen-7-yloxy)-N-(4-
((E)-3- (3,4,5-trimethoxy-
phenyl)acryloyl)phenyl)
acetamide
(4- (4- aryl)-1H- pyrrol-3-yl) Synthetic - - 4.1 μg/mL Antibacterial Divakar and Shanmugam
(pyren-1-yl)meth- (2017)
Anone + (3-chloro)
monocarbonyl curcuminoids Synthetic - ATCC 25923 250 mg/mL Antibacterial Ud Din et al. (2017)
2-(2-Hydroxyphenyl)-5- Synthetic Claisen–Schmidt – 100 μg mL Antibacterial Patel et al. (2017)
methyl-3-(4-(thiophen-
2-yl)-6-(4- methyl-
phenyl)-pyrimidin-2-yl)
thiazolidin-4-one;
3-Chloro-4-(4-hydroxy-
3-methoxyphenyl)-1-(4-
(thiophen-2- yl)-6-(4-
methyl-phenyl)-pyrimidin-
2-yl)azetidin-2-one
(2E,20 E)-3,30 -(3,30 Synthetic Claisen–Schmidt MTCC 96 8 μg/mL Antibacterial Yusuf et al. (2017)
-(butane-1,4-diylbis(oxy))
bis(3,1- phenylene))bis(1-
(thiophen-2-yl)prop-2-en-
1-one)
(2E,20 E)-3,30 -(3,30
-(pentane-1,5-diylbis(oxy))
bis(3,1- phenylene))bis(1-
(thiophen-2-yl)prop-2-en-
1-one)
Chalcones derived from Synthetic – – 9–14 mm Antibacterial Kumar et al. (2017b)
Pyrimidines
Phenylpropenone pyrrolyl Synthetic – – 6–11 mm Antibacterial Kumar et al. (2017a)
Chalcone
Chalcones with a triazine Synthetic – MTCC 96 7–13 mm Antibacterial Mahmoodi et al. (2017)
nucleus (P1–P3, P5, P6,
S6)

13
Page 11 of 30 1
 1

Table 3  (continued)
Chalcone Type Synthesis technique S. aureus strain (s) MIC/Inhibition Zone Activity Quote

Derivatives of Synthetic Claisen–Schmidt ATCC 29213 14 mm Antibacterial Kocyigit et al. (2017)

(3ar,4S,7R,7as)-2-(4-
Page 12 of 30

((E)-3-(3- aryl)acryloyl)
phenyl)-3a,4,7,7a-
tetrahydro-1H-4,7-

13
methanoisoindole1,3(2H)-
dione (7e, 7l, 7m and 7n)
(2E)-3-(2,6- dichlorophenyl)- Synthetic – – 50 mg/mL Antibacterial Sadgir et al. (2020)
1-(4-methoxyphenyl) prop-
2-en-1-one
Chalcones derived from Synthetic – – 12.5–25 µg/ml Antibacterial Desai and Sastry (2017)
Pyrazoline
6,6-dimethyl3-aryl-3′,4′,6,7- Synthetic Claisen–Schmidt ATCC 29213 16 mm Antibacterial Ergüntürk et al. (2017)
tetrahydro-1′H,3H-
spiro[benzofuran-2,2′-
naphthalene]-1′,4(5H)-
dione (5a)
2-Pyrazoline (5f) Synthetic Claisen–Schmidt MTCC 737 10 mg/mL Antibacterial Lokeshwari et al. (2017)
2-bromo-4-[3-(2- Synthetic – FNCC 0047 7.25 mm Antibacterial Setyawati et al. (2017)
hydroxyphenyl)-4,5-
dihydro-1h-pyrazol-5-yl]-
6-methoxyphenol
1-[5-(3-bromo-4-hydroxy-
5-methoxyphenyl)-3-(2-
hydrophenyl]-4,5-dihydro-
1H-pyrazol-1-yl)ethanone
Cis-3-4-dihydrohamacanthin Synthetic – RN4220; MRSA 252; 12.5 µg/mL; 6.25 µg/mL Antibacterial Labrière et al. (2017)
B; ATCC 29213
Bromodeoxytopsentin
(2E,2′E)-3,3′-(octane-1,8- Synthetic Claisen–Schmidt MTCC 96 8 μg/mL Antibacterial Yusuf et al. (2017)
diylbis(oxy))bis(3,1- phe-
nylene))bis(1-phenylprop-
2-ene-1-one)
1,12-bis(3-(1,3-diphenyl-
4,5-dihydro-1H-pyrazol5-
yl)phenoxy)dodecane
Jaceosidin; Synthetic – ATCC 43,300, 32–128 µg/mL Antibacterial Kumar et al. (2016)
5,7,4′-triacetoxy jaceosidin VRS 10, NRS 17
NRS 1
3′-formyl-2′,4′,6′- Synthetic – ATCC 29,213 17.4 μM Antibacterial Zaki et al. (2016)
trihydroxydihydrochalcone MRSA 33,591 36.6 μM
3 Biotech (2023) 13:1
 Table 3  (continued)
Chalcone Type Synthesis technique S. aureus strain (s) MIC/Inhibition Zone Activity Quote

Quinoline scaffold (3b, 3d, Synthetic Claisen–Schmidt - 200 µg/mL Antibacterial Dave and Rahatgaonkar
3g, 3h–j) (2016)
Ferrocenyl chalcones with Synthetic Claisen–Schmidt ATCC 25923 0.625–5 µg/mL Antibacterial Muškinja et al. (2016)
3 Biotech (2023) 13:1

O-alkylated vanillins
Complex Chalcones (3e, 3l) Synthetic – ATCC 43300 21.8% Redução de Antibacterial Patil et al. (2016)
crescimento
(E)-3-{5-[(2-Benzoylben- Synthetic Claisen–Schmidt – 55 µg/mL Antibacterial SHankar et al. (2016)
zofuran-5-yl)methyl]-2- 34 µg/mL
hydroxyphenyl}-
1-(3,4-dichlorophenyl)
prop-2-en-1- one;
{5-[3-(8-Fluoro-4-phenyl-
2,3-dihydro-1H-benzo- [b]
[1,4]diazepin-2-yl)-4-hy-
droxybenzyl]benzofuran2-
yl}(phenyl)methanone
(4-Bromo-6,7-dimethoxy- Synthetic – ATCC 6538 200–400 µg/mL No significant antibacte- Patel et al. (2016)
1,1-dioxido-3,4-dihydro- rial activity
2H-benzo[e][1,2]thiazin-
3-yl)(3-chlorophenyl)
methanone
(4-Bromo-6,7-dimethoxy-
1,1-dioxido-3,4-dihydro-
2H-benzo[e][1,2]thiazin-
3-yl)(3-bromophenyl)
methanone
(4-Bromo-2-ethyl-
6,7-dimethoxy-1,1-dioxido-
3,4-dihydro-2H-benzo[e]
[1,2]thiazin-3-yl)(3-bromo-
phenyl)methanone
Carbazole-based Chalcones Synthetic Claisen–Schmidt ATCC 6538 20 µg/mL Antibacterial Ashok et al. (2016)
(3a, 3h, 3i, 4a, 4h, 4i, 5a,
5h, 5i)
Glabridin-chalcone hybrid Synthetic Claisen–Schmidt MTCC-96 12,5 µg/mL Antibacterial Kapkoti et al. (2016)
molecules (6h, 7e, 8f) MRSA-ST 2071
Chalcones derived from Synthetic – 4220 1–64 μg/mL Antibacterial Killeen et al. (2016)
1,3-diaryl pyrazole (6g, 6l
and 7l)
Chalcones Derivatives (4ª, Synthetic Claisen–Schmidt 4220, 209 and 503 2 μg/mL Antibacterial Wei et al. (2016)
4f)

13
Page 13 of 30 1
 1

Table 3  (continued)
Chalcone Type Synthesis technique S. aureus strain (s) MIC/Inhibition Zone Activity Quote

1-[7-(diethylamino)-2H- Synthetic Claisen–Schmidt – 100 µg/mL Antibacterial Himangini and Pathak

chromen-2on]-3-(p- (2016)
Page 14 of 30

chlorophenyl)-2-propen-1-
one one;
1-[7-(diethylamino)-2H-

13
chromen-2on]-3-(p-
fluorophenyl)-2-propen-
1-one
4,5-Dihydro-3-(1-benzyl-1H- Synthetic Claisen–Schmidt RCMB 010028 23.4 mm Antibacterial Abo-Salem et al. (2016)
indol-3-yl)-5-(naphthalene-
2-yl) isoxazole
1,3-thiazine compounds Synthetic Claisen–Schmidt – 09–15 mm Antibacterial Babu et al. (2015)
with a Schiff base portion
(5a-5e)
2,8- bis(2,4-Dichlorophenyl)- Synthetic Claisen–Schmidt ATCC 29737 12.5 µg/mL Antibacterial Husain et al. (2015)
4H,6H-pyrano[3,2-g]
chromene-4,6-dione
2-Chloro-N-{4-[3- Synthetic Claisen–Schmidt – 9 mm Antibacterial Jayaramu and Maralihallia
(substitutedphenyl)- (2015)
acryloyl]-phenyl}-aceta-
mide
3-(4′-N,N-dimethyl amino Synthetic Claisen–Schmidt MTCC 96 5–20 µg/mL Antibacterial Raju et al. (2015)
phenyl)-5-(2″, 2″-dime-
thyl, 7″-hydroxy chroman)
isoxazole/3-(3′,4′-chloro-
phenyl)-5-(2″, 2″-dimethyl,
7″-hydroxy chroman)
isoxazole/3-(4′-methoxy-
phenyl)-5-(2″, 2″-dimethyl,
7″-hydroxy chroman)
isoxazole/3-(4′-cyano
phenyl)-5-(2″, 2″-dime-
thyl, 7″-hydroxy chroman)
isoxazole
3 Biotech (2023) 13:1
 Table 3  (continued)
Chalcone Type Synthesis technique S. aureus strain (s) MIC/Inhibition Zone Activity Quote

trans-3-(1H-indol-3-yl)-1- Synthetic Claisen–Schmidt ATCC 96 12.5–50 mg mL Antibacterial Gaur et al. (2015)

(40-benzyloxyphenyl)- MRSA
2-propen-1-one (2),
3 Biotech (2023) 13:1

1-(400-biphenyl)-3-(30
40-dihydroxyphenyl)-
2-propen-1-one (11),
1-(400-hydroxy-
300-methylphenyl)-3-(40
-hydroxyphenyl)-2-
propen-1-one (14), 3-(40
-chlorophenyl)-1-(400-
hydroxyphenyl)-2-propen-
1-one (17), LTG-oxime
6H-benzo[c]chromen-6-ones Synthetic Claisen–Schmidt ATCC 9144 0.625 μg/mL Antibacterial Mazimba (2015)
and Diazepines (10a,b)
Chalcone Synthetic – USA 300; 53.15 μM Antibacterial and anti- Zhang et al. (2017)
acquired USA 300 ΔSRTA​ 76 μM biofilm
Apchal and Achlopheny Synthetic Claisen–Schmidt ATCC 25923, 10, 70% synergism of Antibacterial. Synergism Siqueira et al. (2020)
1199B, K2068 gentamicin when and antagonism were
associated with Apchal observed
and loss of synergism
when associated with
Aclo-phenyl
Apchal and Achlophenyl Synthetic Claisen–Schmidt SA-1199B; K2068 Synergism with Nor- Efflux pump inhibitor Siqueira et al. (2020)
floxacin and cipro-
floxacin; synergism
with ciprofloxacin and
ethidium bromide
1,3- Bis-(2-hydroxy-phenyl)- Synthetic – MRSA ATCC 43,300, 37.5 ± 13.2 μg/mL; Antibacterial Božić et al. (2015)
propenone, 3-(3-hydroxy- MRSA CC5, CC8, 97.5 ± 27.5 μg/mL;
phenyl)-1-(2-hydroxy- CC45, CC80, CC152 110.8 ± 21.1 μg/mL
phenyl)-propenone e
3-(4-hydroxy-phenyl)-
1-(2-hydroxy-phenyl)-
propenone
Chalcones and derivatives Synthetic Claisen–Schmidt Newman (MSSA); MN8 3.12 μg/mL; Antibacterial, anti- Zhang et al. (2018a, b)
(6s e12a) (MRSA); NRS70 6.25 μg/mL: biofilm
(MRSA) 0.8 μg/mL

13
Page 15 of 30 1
 1

Table 3  (continued)
Chalcone Type Synthesis technique S. aureus strain (s) MIC/Inhibition Zone Activity Quote

(E)-N-(3-Aminopropyl)-2- Synthetic – ATCC29213, MRSA 1.56–3.13 μg/mL Antibacterial Lin et al. (2020)
(5-((3-methylbut-2-en- N315, MRSA
Page 16 of 30

1-yl)oxy)-2-(3-(4-((3- NCTC10442
methylbut-2-e n-1-yl)oxy)
phenyl)acryloyl)phenoxy)

13
acetamide
Thiazolyl-pyrazoline deriva- Synthetic Claisen–Schmidt MSSA (ATCC 25,923), 62.5 µg/mL; Antibacterial Cuartas et al. (2020)
tives (7 a) MRSA (ATCC 125 µg/mL;
43,300), VISA 31.5 µg/mL;
Derivatives of benzo[4,5] Synthetic – ATCC 6538 > 1600 µg/mL Inactive for antibacterial Bassin et al. (2017)
isothiazolo[2,3-a]pyrazine- activity
6,6-dioxide
Derivatives of Synthetic – ATCC 43,300, Clinical > 128 µg/mL Antibacterial Kumar et al. (2016)
2′,6′-dihydroxy-4′- isolate, VRS 10, NRS 64 µg/mL
methoxy-3′,5′-dimethyl 17, NRS 1 32 µg/mL
chalcone (10)
Derivatives of (E)-3-(4- Synthetic – ATCC 29,737 25.4 mm Antibacterial Bhirud et al. (2020)
bromophenyl)-1-(p-tolyl) 27.2 mm
prop-2-en-1-one (3a, 3e, 3j) 26.4 mm
7,4′-dihydroxy-8,3′- Synthetic Claisen–Schmidt MRSA, 15.4 μM Antibacterial Kwesiga et al. (2020)
diprenylflavone and ATCC 43,300 20.5 μM
erysubin F
(2Z)-3-(3-nitrophenyl)-1- Synthetic Claisen–Schmidt ATCC 12,598 12.5 g/mL Antibacterial Sivasankerreddy et al.
{4-[(E)-(piperidin-1-yl) (2018)
diazenyl]phenyl}prop-2-
en-1-one
Xanthohumol, naringenin, Synthetic – PCM 2054 3.57 mm Antibacterial Stompor and Zarowska
and chalconaringenin 3.77 mm (2016)
1.92 mm
2′-Hydroxychalcone; Synthetic Claisen–Schmidt D1 0.26 ± 0.09, Antibacterial Gładkowski et al. (2019)
2 0-Hydroxy-2-methoxychal- 0 ± 0.03,
cone; 0.88 ± 0.10
2 0-Hydroxy-4-methoxychal- 0 ± 0.04
cone;
2 0-Hydroxy-40 -methoxy-
chalcone-3-yl)(3-bromo-
phenyl)methanone
4-Hydroxyphenyl Synthetic Claisen–Schmidt – 5 µg/mL Antibacterial Desai et al. (2017)
3-Hydroxyphenyl 10 µg/mL
Aryl substituted dihydrotria- Synthetic – 4220 0.5 µg/mL Antibacterial Zhang et al. (2018a)
zine derivatives (17h) QRSA CCARM 3505
3 Biotech (2023) 13:1
 Table 3  (continued)
Chalcone Type Synthesis technique S. aureus strain (s) MIC/Inhibition Zone Activity Quote

Derivatives of 1,2,3-triazoles Synthetic Claisen–Schmidt – MIC decrease in 55% Antibacterial Syed-Aly et al. (2015)
(25)
Derivatives of (2-(Pyridinyl) Synthetic – MRSA Decrease of 75% Antibacterial Gibson et al. (2017)
3 Biotech (2023) 13:1

methylene)-1-tetralone
Chalcones (5h)
(E)-N-(4-(3-(4-Chlorophe- Synthetic – IFO 3060 2.0 mg/mL Antibacterial and anti- El-Messery et al. (2018)
nyl)acryloyl)phenyl)-3- 2.4–8.6 mg/mL biofilm
(piperidin-1-yl)propana-
mide,
(E)-N-(4-(3-(4-Methoxy-
phenyl)acryloyl)phenyl)-3-
(piperidin-1-yl)propana-
mide,
(E)-3-(Piperidin-1-yl)-
N-(4-(3-(3,4,5-trimethoxy-
phenyl)acryloyl)phenyl)
propanamide

13
Page 17 of 30 1
 1

Table 3  (continued)
Chalcone Type Synthesis technique S. aureus strain (s) MIC/Inhibition Zone Activity Quote

(2E)-3-(4-{[1-(2-chloro-4- Synthetic – ATCC 25323 6.25 µg/mL Antibacterial Kant et al. (2016)
fluorophenyl)-1H-1,2,3- 12.5 µg/mL
Page 18 of 30

triazol-4-yl]methoxy}-3-
methoxyphenyl)-1-(2-
hydroxy-4,6-dimethoxy-

13
phenyl)prop-2-en-1-one,
(2E)-3-(4-{[1-(2,4-
difluorophenyl)-1H-
1,2,3-triazol-4-yl]
methoxy}-3-methoxy-
phenyl)-1- (2-hydroxy-
4,6-dimethoxyphenyl)
prop-2-en-1-one,
(2E)-3-(4-{[1-(2-
chlorophenyl)-1H-
1,2,3-triazol-4-yl]
methoxy}-3-methoxy-
phenyl)-1-(2- hydroxy-
4,6-dimethoxyphenyl)
prop-2-en-1-one,
(2E)-3-[3,4-bis({[1-(2,4-
difluorophenyl)-1H-1,2,3-
triazol-4-yl]methoxy})
phenyl]-1-(2- hydroxy-
4,6-dimethoxyphenyl)
prop-2-en-1-one,
2-[3,4-bis({[1-(4-
chlorophenyl)-1H-1,2,3-
triazol-4-yl]methoxy})
phenyl]-5,7-dimethoxy4H-
chromen-4-one
4′-hydroxy-4-methyl chal- Synthetic – ATCC 29213 32 μg/mL Antibacterial Evranos-Aksöz et al.
cone (2015)
Asymmetric heterocyclic Synthetic – ATCC 25923 65–95% of zone of Antibacterial El-Hashash et al. (2015)
chalcone derivatives and inhibition
heterocyclic compounds (4,
6, 7, 9)
Derivatives of 3-hydroxy- Synthetic – MLS-16 7.8–15.6 µg/mL Antibacterial Bingi et al. (2015)
6-(hydroxymethyl)-2-(2- MTCC 2940
phenyl-4H-chromen-4-yl)-
4H-pyran-4-ones (3a, 3e,
3f e 3 l)
3 Biotech (2023) 13:1
 Table 3  (continued)
Chalcone Type Synthesis technique S. aureus strain (s) MIC/Inhibition Zone Activity Quote

Chalcona derivative: (4[(1E)- Synthetic Claisen–Schmidt ATCC 2592 (MRSA) 0.12 μM Antibacterial and antibi- Emeri et al. (2019)
3-(pentyloxy)buta-1,3- ATCC 33591 ofilm
dien-1-yl]benzene-1,2-diol
3 Biotech (2023) 13:1

N-(5a-chloro, Synthetic – SA-29213; SA-1199;SA- 50 (mg/L); 25(mg/L); Antibacterial Gupta et al. (2019)
8a-triflouromethyl)-benzyl- Derived from the natural 1199B*; SA-K1758; 50(mg/L); 25 (mg/L); *NorA efflux pump
N, 1a-dihydro-2H-O, Chalcone Isoliquiriti- MRSA-P4423; MRSA- 50(mg/L); 25(mg/L); inhibitor
N-isoliquiritigeninoxazine genin (ISL) P4627; MRSA-P4620; 25 (mg/L); 50(mg/L);
(IMRG4) MRSA-B10760; 25(mg/L); 50 (mg/L);
MRSA-ST315; VISA- 50(mg/L)
ST207; VISA-ST1745
(2E)-1-(3′, -methoxy-4′,- Synthetic Claisen–Schmidt ATCC 25923; ≤ 512 mg/mL Antibacterial Garcia et al. (2020)
hydroxyphenyl)-3-(3- 10
nitrophenyl) prop-2-en1-
one
(AVMNB)
(2E)-1-(3′, -methoxy-4′,- Synthetic Claisen–Schmidt ATCC 25923; MIC↑ Antagonistic with Garcia et al. (2020)
hydroxyphenyl)-3-(3- 10 Cephalexin and Gen-
nitrophenyl) prop-2-en1- tamicin antibiotics
one
(AVMNB)
2E-1-(2ʹ-hidroxi-3ʹ,4ʹ,6ʹ- Synthetic Claisen–Schmidt 358 1024 µg/L Inactive for antibacterial Teixeira et al. (2019)
trimetoxifenil)-3-(fenil)- Derived from the MIC↓ activity
prop-2-en-1-ona natural compound: Antibiotic modulator:
(HYTPHENYL) 2-hydroxy-3,4,6-tri- Synergism with the
methoxyacetophenone antibiotic Amikacin
(E)-3-(2-methylpyrimidin- Synthetic Claisen–Schmidt – Concentration of 25 μg: Antibacterial Twinkle et al. (2020)
5-yl)-1-ferroceynlprop- 19 mm
2-en-1-one Concentration of 50 μg:
(MPFP) 24 mm
Concentration of 75 μg:
31 mm
Cationic derivatives of Synthetic Claisen–Schmidt M1-M9 Ranged from 0.25 Antibacterial and syner- (CHU et al., 2018)
Chalcones: MRSA –32 µg/mL gism with Norfloxacin
5a; 5s; 5b; 5c; 5d, 5g, 5l, 5p, and Colistin
5q; 5r; 5z; 5ab
Cationic molecule 5g Synthetic Claisen–Schmidt ATCC29213 128 µg/mL Anti-biofilm (CHU et al., 2018)

13
Page 19 of 30 1
 1

Table 3  (continued)
Chalcone Type Synthesis technique S. aureus strain (s) MIC/Inhibition Zone Activity Quote

Chalcones derivatives: Synthetic – – Concentration of 100 μg/ Antibacterial Babu and Selvaraju
(E)-2-(4-acetamidophenoxy)- mL: 9; 10 mm (2020)
Page 20 of 30

N-(3-(3-(4-methoxyphenyl) Concentration of 200 μg/

acryloyl)phenyl)acetamide mL: 15 mm; 13 mm
(5e);

13
(E)-2-(4-acetamidophenoxy)-
N-(3-(3-(4-chlorophenyl)
acryloyl) phenyl)acetamide
(5b)
Chalcones-Sulfonamides Synthetic Claisen–Schmidt Resistant clinical isolates > 57 mcM Inactive for antibacterial Castaño et al. (2019)
5/6, 8a-f and 9a-f activity
(N = 12 derivatives)
Thiazole-based Chalcone Synthetic – IFO 3060 1 μg/mL Antibacterial Alrohily et al. (2019)
(Derivative): Compound 18
Ferrocenyl Chalcone Deriva- Synthetic – ATCC 9144 1.349 × ­10–8 M/mL Significant antibacterial Liu et al. (2019)
tives: 1.268 × ­10–7 M/mL
Zn (II)
(H1; H5)
Derivative: Synthetic Synthesized and char- ATCC 12600 250 μg/mL Antibacterial Zainuri et al. (2017)
(E)-1-(4-brom acterized using XRD,
ophenyl)-3-(4-iodophenyl) FT-IR1 H and 13 C
prop-2-en-1-one NMR
Ferrocenyl Chalcone Deriva- Synthetic – MRSA, ATCC 43300 Concentração de 3 g/L: Antibacterial Liu et al. (2018)
tives: 11–22 mm
3a2,3a7 e 3b6
Chalcones derivatives: Synthetic Claisen–Schmidt ATCC-9144 08 µg/mL Antibacterial Gopi et al. (2016)
4a; 4e; 4h 08 µg/mL
04 µg/mL
(E)-1-(4-Bromophenyl)-3- Synthetic Claisen–Schmidt ATCC 12600 500 µg/mL Antibacterial Thanigaimani et al. (2015)
(napthalen-2-yl)prop-2-en-
1-one
Derivatives if indolyl-4H- Synthetic Claisen–Schmidt ATCC 700699 9.3 µg/mL Antibacterial Subbareddy et al. (2018)
chromene-phenylprop-2-
en-1-one (5g; 5h)
Chalcone derivative: Synthetic Claisen–Schmidt – 3.9 µg/mL Antibacterial El-Desoky et al, (2018)
1-hydroxynaphth-2-yl pyra-
zoline (6b)
Chalcone derivative: Pyra- Synthetic Claisen–Schmidt MTCC 3160 6.5 µg/mL Antibacterial Mishra et al. (2017)
zoles (5j; 5h)
3 Biotech (2023) 13:1
 3 Biotech (2023) 13:1 Page 21 of 30 1

benzaldehydes and acetophenones that can be combined,

Low antibacterial activ- Yusuf and Solanki (2017)

providing the structural variety intended (Ducki et al. 1998;

Inactive for antibacterial Ramírez-Prada et al.

Prasad et al. (2019) Narender and Papi Reddy 2007).

Antibacterial activity of natural Chalcones

(2017)
Quote

Generally, Chalcones can be categorized into single and

hybrid Chalcones with the central skeleton of 1,3-diaryl-
2-propen-1-one. In plants, Chalcones (cis and trans) are
intermediates in the biosynthesis of flavonoids, which
increased interest in this substance, and in 1910 occurred
Antibacterial

its first isolation in the laboratory (Shimokoriyama 1962;

activity
Activity

Ferreira et al. 2018). Chalcones can be found in dicotyledon-

ity

ous plants, some monocotyledons, pteridophytes and gym-

nosperms, but they are synthesized as main components in
the Leguminosae, Asteracea and Moracea families, which
MIC/Inhibition Zone

are currently still used in folk medicine in the form of teas

(Banoth and Thatikonda 2020).
> 1000 µg/mL

16–32 µg/mL

The biological potential of Chalcones has been inves-

500 µg/mL

tigated since the 1940s, but it was only in the 1970s that
researchers became more interested in exploring natural
Chalcones when they showed anti-parasitic activities (Nowa-
kowska 2007). With the discovery of antiparasitic activ-
ATCC 43300 (MRSA)
ATCC 25923 (MSSA)

ity, the search for more biological activities of Chalcones

S. aureus strain (s)

intensified, since then researchers around the world isolate

and test natural Chalcones for various purposes, especially
a) The spaces filled with (–) mean that the information was absent from the article or was not clear
NCIM 2079

antibacterial activities, which is an emerging issue in a glo-

balized world with so many human deaths by increasingly
resistant bacteria.
–

In this context, Moreno et al. (2015), solated the Chal-

cones 2ʹ,4ʹ-dihydroxychalcone and 2ʹ,4ʹ-dihydroxy-3ʹ-
Synthesis technique

methoxychalcone from the Zuccagnia punctata plant against

Claisen–Schmidt

Claisen–Schmidt

Claisen–Schmidt

a standard strain of S. aureus and a Methicillin-resistant

strain (MRSA), which exhibited antibacterial potential
with MIC of 250 µg mL. In the following year, Costa et al.
(2016), tested the antibacterial potential of the natural Chal-
cone 20-hydroxy-4,40,60-trimethoxychalcone isolated from
the botanical species Piper hyspidium, which obtained an
MIC of 125 µg/mL showing potential antibacterial activity.
In the same way Mariani et al. (2016) tested the antibacterial
potential of natural Chalcone 4,4′,6′ trihydroxy 3 methoxy
Synthetic

Synthetic

Synthetic

3′ pentene chalcone isolated from Elatostema parasiticum

which exhibited an MIC of 7.8 μg/mL which was considered
Type

to be good antimicrobial activity against a S. aureus clinic

strain.
chlorophenyl)prop-2-en-1-

6-(4-chlorophenyl)pyrimi-
4-[(E){[4-(4-bromophenyl)-

In 2018, Chalcone 2′,4′-dihydroxychalcone was isolated

din-2-yl]imino}methyl]
(4-bromophenyl)-1-(4-

amino]chalcones 8a–f
Derivative of Chalcone

benzene-1,3-diol (IJ)
[(Chloroquinolin-4-yl)

from aerial parts of Zuccagnia punctata which showed

Table 3  (continued)

Bichalcones 8 (a–h)

noticeable antibacterial and anti-biofilm activity against a

series of S. aureus strains, reaching MIC of 25 µg/mL and
12.5 µg/mL, respectively (Nuño et al. 2018). In the follow-
Chalcone

one (I):

ing year, Meier et al. (2019) isolated Chalcone Xantoangelol

from the fruits of Amorpha fruticosa which demonstrated

13
1 Page 22 of 30 3 Biotech (2023) 13:1

a potent bactericidal effect against MRSA strain, reaching against two strains of S. aureus carrying an important viru-
MIC of 12.5 µM. lence-related enzyme, Sortase A (SrtA). The use of chalcone
In Table 2 below, studies in which natural Chalcones do against USA 300 and USA 300 ΔSRTA strains expressed
not show clinically relevant antibacterial activity can be an MIC of 53.15 μM and 76 μM, respectively, which can be
observed, but they were able to inhibit known resistance considered a good anti-virulence strategy in the fight against
mechanisms, such as efflux pumps. Results like these are infections by S. aureus.
demonstrated in the study by Rezende-Júnior et al. (2020). In the frame built to show all the studies included in this
In the aforementioned study, the natural Chalcone 3′,4′-dihy- review, it is possible to observe that there are also many
droxy, 3,4,4′-trimethoxy-chalcone (4) was isolated from the works using hybrid Chalcones. Molecular hybridization is an
botanical species Arrabidaea brachypoda and tested its efficient strategy, widely used for drug design. Hybrid mol-
antibacterial effect against a series of clinical strains of S. ecules or compounds can provide more biological targets,
aureus, including a strain carrying the NorA efflux pump, which facilitates the achievement of the desired bioactivity
SA-1199B. In the direct antibacterial activity clinical trial, (Dan and Dai 2019). Therefore, in the study by Kapkoti et al.
results were determined as clinically irrelevant with an MIC (2016) ome hybrid molecules of Glabridin-chalcone (6h, 7e,
of ≥ 1024 μg/mL. However, in the Ethidium Bromide (BrEt) 8f) were synthesized and tested their antibacterial potential
trial, natural Chalcone reduced the MIC to 16 µg/mL, acting against MTCC-96 and MRSA-ST 2071 strains, obtaining
as a potential efflux pump inhibitor. a MIC of 12.5 µg/mL, among all compounds tested, com-
pound 8H exhibited marked synergism and reduction of
Antibacterial activity of synthetic Chalcones up to 16 times in MICs with Norfloxacin (FICI range from
and derivatives 0.312 to 0.375).
When it comes to synergism, it was observed that sev-
Due to advances in synthetic organic chemistry, it is pos- eral articles report antibiotic potentiation by synthetic
sible to obtain bioactive compounds with a diversity of sub- Chalcones, such as the work carried out by Siqueira et al.
stituents in an increasingly versatile way, such as several (2020). The Chalcones (2E)-1-(4′-aminophenyl)-3-(phenyl)-
Chalcones that are synthesized from the manipulation of prop-2-en-1-one (APCHAL) and (2E)-1-(4′-aminophenyl)-
the aromatic rings of natural Chalcones (Fonseca 2012). The 3-(4-Chlorophenyl)-prop-2-en-1-one (ACLO-PHENYL)
Claisen–Schmidt condensation methodology between aryl were synthesized by Claisen–Schmidt condensation and
ketones and benzaldehyde derivatives is revealed as the most tested against a number of standard and multidrug-resistant
used methodological strategy for the construction of various strains. It was observed that Chalcone Apchal reduced the
chalconic nuclei (Winter 2016). MIC by up to 70% of the antibiotic Gentamicin (synergism)
A series of Chalcones and derivatives were synthesized while expressing antagonism with the antibiotic Penicillin.
by the Claisen–Schmidt condensation in the study by Zhang Regarding Chalcone Aclo-phenyl, due to the addition of a
et al. (2018a, b). The antibacterial evaluation revealed that chlorine group in the substance, a loss of synergism with
an A ring substituted with R1 hydroxy groups in the 6 series Gentamicin was observed.
of Chalcones produced active compounds with considerable The Chalcones mentioned above were also tested as
antibacterial activity, such as the compound 6s ((E)-3-(4- potential efflux pump inhibitors on SA-1199B strain car-
(Diethylamino)phenyl)-1-(2,4-dihydroxyphenyl)prop-2-en- rying the NorA efflux pump and K-2068 strain carrying the
1-one) which exhibited an MIC of 3.12 μg/mL and 6.25 MepA efflux pump. In the evaluation of inhibition of this
μg/mL against MSSA and MRSA strains, respectively. The resistance mechanism, both Chalcones exhibited a synergis-
α,β-unsaturated ligand between rings A and B was shown to tic effect with the antibiotics Norfloxacin and Ciprofloxacin,
be important for antibacterial activity. although Aclo-phenyl is less pronounced. On the other hand,
Cuartas et al. (2020) also tested the potential of Chalcones Aphcal showed synergism with both Ciprofloxacin and BrEt,
against MSSA and MRSA strains. Chalcones derived from showing good results with the inhibition of the MepA efflux
N-substituted pyrazolines proved to be excellent candidates pump. The results also demonstrate that both compounds
for the development of new antimicrobials. The compound bind approximately to the same region of the 1199B binding
5-{2-[Bis(2-chloroethyl)amino]-4-chlorothiazol-5-yl}-3-(4- site and that this region overlaps with the preferred binding
chlorophenyl)-4,5-dihydro-1H-pyrazole-1-carbaldehyde (7a) region of Norfloxacin. Based on these results, the authors
exhibited a MIC of 61.25 µg/mL for MSSA and 125 µg/mL state that Chalcone Aphcal can significantly contribute to
for MRSA, exhibiting a lower MIC value (31.5 µg/mL) for the prophylaxis or therapy of diseases caused by multidrug-
the VISA strain (Vancomycin—intermediate Staphylococ- resistant S. aureus.
cus aureus). All the studies, presented and their relevance to the scien-
Zhang et al. (2017), obtained good antibacterial and tific community in terms of public health, reveal the impor-
anti-biofilm activity of a commercially purchased chalcone tance of investigating natural compounds and the synthesis

13
3 Biotech (2023) 13:1 Page 23 of 30 1

of new substances to solve the problem of bacterial resist- have been worrying global health agencies, as these char-
ance worldwide, as well as proving that the bacterium S. acteristics impose a barrier to existing treatments, which
aureus is currently one of the bacteria with the greatest many of these treatments have suffered decreases in terms
investigative focus, given all the complications generated in of use and effectiveness (Anvisa 2018). One of the effective
public health and in the global economy (Table 3). resistance mechanisms employed by S. aureus is the active
pumping of antimicrobials through membrane transporters,
Chalcones synthesis known as efflux pumps (Jang 2016; Rao et al. 2018). Efflux
pumps are proteins capable of extruding several types of
Several methodologies are reported in the literature for the chemically different substrates, mainly antibiotics (Costa
preparation of Chalcones, but the best known and most used et al. 2013; Hassanzadeh et al. 2020), contributing signifi-
is the synthesis through the Claisen–Shmidt condensation, cantly to a high level of resistance.
in which the reaction of a chosen derivative of acetophe- With the knowledge about the functionality of efflux
none with suitable aromatic aldehydes occurs, using ethanol pumps and with the goal of reversing bacterial resistance
or methanol as solvent and sodium hydroxide or potassium through the inhibition of this mechanism, new Chalcones
hydroxide as catalyst or different reaction conditions, such as are being synthesized for the investigation of their inhibitory
aldol condensation in solid phase, by microwave and without potential, which can act as efflux pump inhibitors (EPIs)
the use of solvent. It is a very simple and convenient meth- (Labrière et al. 2017; Siqueira et al. 2020). The administra-
odology although, in some cases, it results in a lower income tion of antibiotics and EPIs simultaneously can reduce the
(Mahapatra et al. 2015; Souza 2014). amount needed of a drug to achieve the same effect (Prasch
The general steps for the synthesis of Chalcones using and Bucar 2015; Seukep et al. 2020). Many studies reported
Claisen Schmdth condensation start with aldol condensa- in the synthesis tables show the activity of synergisms or
tion followed by basic dehydration (Lindoso and Lindoso antibiotic potentiators of several Chalcones, such as the
2009). The initial step of reaction is the deprotonation of works carried out by Vásquez-Martínez et al. (2019) and
the ketone group, where the basic catalyst removes the acid Ferraz et al. (2020).
alpha hydrogen of the molecule to produce a carbanion In the findings of this review, the following studies that
which can be stabilized by resonance. From this, a nucleo- worked with pumps were reported: (1) NorA: belonging to
philic attack occurs against the carbonyl carbon of the alde- the largest and oldest pump family, the Major Facilitator
hyde, structuring a tetrahedral intermediate (alkoxide ion). Superfamily (MFS) and is present in the SA-199B strain.;
This intermediate is protonated by a hydrogen in water gen- (2) MepA: belonging to the Multidrug and Compound
erating the condensation product and regenerating the basic Extrusion Family (Multidrug and Toxic Compound Extru-
catalyst. The condensation product occurs by dehydration sion—MATE), this pump is expressed in K-2068 strains,
and for this to happen it is necessary to remove a hydrogen both are reported in the works of Rezende-Júnior et al.
from the alpha position to result in the enolate ion, which (2020), Siqueira et al. (2020), Rocha et al. (2021), Xavier
by equilibrium eliminates the OH– group, thus forming the et al. (2021) and Da Silva et al. (2021); (3) MsrA: present
Chalcone (Chiaradia 2010). in the RN-4220 S. aureus strain and belongs to the ABC
Other less common methodologies in the synthesis of protein group, this pump was used in the studies by Labrière
Chalcones are described in the literature such as Heck, et al. (2017), Xavier et al. (2021) and Rezende-Júnior et al.
Sonogashira, and SuzukiMiyaura coupling, Friedel–Crafts (2020); This last author also worked with the efflux pumps
reaction. However, there is an advantage in using the aldol (4) QacA/B present in K4414 e (5) QacC overexpressed in
condensation methodology (Claisen–schmidt) which is its K4100 strain, belonging to the family of transporters MFS
accessibility when compared to the others, as it does not and SMR, respectively.
require high temperatures or expensive catalysts. Differ- The works mentioned above, for the most part, presented
ent methodologies, such as coupling reactions, can become relevant results for the research, either by the inhibition of
inconvenient by causing environmental impacts caused by this mechanism by Chalcones or by the reduction of the MIC
metals that are used in the process (Mahapatra et al. 2015; of the antibiotics used through synergisms, thus potentiating
Souza 2014). the antibiotic activity.

Bacterial resistance and efflux pump Structure–activity relationship

Resistance mechanisms and their inhibition by Chalcones In medicinal chemistry, the term structure–activity rela-
is widely cited by many studies in this review. This is due tionship can be understood as the effect that the chemical
to the emergence of several complex mechanisms and rapid structure of a compound has on its biological activity. The
dissemination of multidrug-resistant microorganisms that main objective of this analysis is to investigate how variation

13
1 Page 24 of 30 3 Biotech (2023) 13:1

in chemical structure can affect the biological potential of the importance of the effects caused by the change in the
a substance or the ligand/receptor affinity (Marino 2014). conformation of a chemical structure or the substitution of
According to Guido et al. (2010), the structure–activity functional groups by others.
relationships can be defined from changes in the prototype In the study by Ramírez-Prada et al. (2017) the anti-
molecule and the evaluation of its subsequent biological bacterial potential of Chalcones and some derivatives is
activities. described. Although the Chalcone [(7-Chloroquinolin-4-yl)
In the study by Kozłowska et al. (2019) the effect of amino]chalcones (8a–f) described in the table did not show
structure on the biological activity of synthetic Chalcones relevant antibacterial activity, compound 6: 3-((7-Chloroqui-
is clearly shown. The author of the work synthesized 18 ami- nolin-4-yl)amino)benzaldehyde which contains the parental
nochalcones and it was possible to observe that the presence benzaldehyde in its structure was the most active of the com-
of an amino group in the meta position with the addition pounds tested, showing inhibitory activity against S. aureus.
of the aromatic ring in compound 14, increased the hydro- The results obtained with aldehyde 6 show that the 7-chloro-
phobicity of the molecule, facilitating penetration of Chal- 4-aminoquinoline nucleus confers antibacterial activity, but
cone into the cells of microorganisms. Babu and Selavaraju this activity is abolished when the nucleus is functionalized
(2020) demonstrated that compounds tested for antibacterial by other chemical groups.
activity that contained the methoxy portion exhibited excel- The structure–activity relationship was summarized based
lent activity. on the antibacterial activity data presented in the summary
In another study also reported in the tables, it demon- tables. It was observed during the analysis of the articles that
strates the synthesis of heterocyclic Chalcones where the the α, β-unsaturated ketone fraction in Chalcones is essen-
reactivity of the produced Chalcones (Chalcones 3) allowed tial for the maintenance of antibacterial activity and that
the construction of several heterocyclic systems such as the change in the A and B rings can drastically change the
pyrazoline, isoxazoline, benzoflavone and benzocoumarin biological activity of a compound. It has also been observed
(El-Desoky et al. 2018). It is possible to observe in the cited that hybrid molecules can significantly improve the desired
study that the modification in the structure of the derivatives antimicrobial activity.
of Chalcones 3b to the corresponding flavonone 9b destroyed
the antibacterial activity; however, the more the modification
to flavone improved in the compound 11b the more the activ-
ity was restored beyond the reference antibiotic. Conclusion
A comparative study was carried out between Chalcones
and pyrazole derivatives about the antibacterial activity This literature review presented the recent advances in the
against S. aureus. There was a great difference in the anti- research of natural and synthetic Chalcones with antibacte-
bacterial potential between these two compounds due to rial potential, organized through informative tables on the
the presence of a hydroxy group in the fourth position of articles that constituted the research sample. The main meth-
the A ring. The 2-pyrazoline functions did not increase the odology used for the synthesis of Chalcones was described,
antimicrobial activity, while the Chalcones showed better as well as the main resistance mechanism reported in the
activity (Evranos-Aksöz at al. 2015a, b). In the study by articles, how it contributes to the multidrug resistance of
Teixeira et al. (2019) the presence of the hydroxy group in S. aureus and the efforts that are being made to inhibit this
the compound 2E-1-(2ʹ-hydroxy-3ʹ,4ʹ,6ʹ-trimethoxyphenyl)- mechanism. Furthermore, the structure–activity relation-
3-(phenyl)-prop-2-en-1-one (HYTPHENYL) did not deter- ship was briefly discussed, to which it can be evidenced
mine any antibacterial activity against S. aureus; however, that several bioactive portions can be incorporated in the
a synergism was noticed when this Chalcone was associated A and B rings and in the α,β-unsaturated ketone fragments.
with the antibiotic Amikacin. This change in antimicrobial It was observed that the compounds based on Chalcones
activity may be related to both the position of the hydroxy showed great antibacterial potential and demonstrated the
group and the presence of the methoxy group in Chalcone. ease of obtaining different skeletons of this group through
The Chalcona derivative (E)-1-(4-bromophenyl)-3-(4- the Claisen–Schmidt condensation methodology. Future
iodophenyl)prop-2-en-1-one reported in the work by Zainuri perspectives in the study of Chalcones may be based on the
et al. (2017) demonstrated good antibacterial activity against investigation and synthesis of new antibacterial drugs based
a standard strain of S. aureus with an MIC of 250 µg/mL. on Chalcones or substances composed of hybrid molecules,
However, when the Iodine group was replaced by naphtha- enrich studies about resistance reversal through inhibition of
lene in the study by Thanigaimani et al. (2015), forming the mechanism cited in the present review and investigate
the compound (E)-1-(4-Bromophenyl)-3-(napthalen-2-yl) the toxicity of Chalcones as antibacterial agentes.
prop-2-en-1-one the antimicrobial activity decreased con- Supplementary Information The online version contains supplemen-
siderably reaching a MIC of 500 µg/mL, demonstrating tary material available at https://d​ oi.o​ rg/1​ 0.1​ 007/s​ 13205-0​ 22-0​ 3398-7.

13
3 Biotech (2023) 13:1 Page 25 of 30 1

Acknowledgements The authors are thankful to the State university pyrazole-chalcone via a simple and convenient protocol using
of Ceará—UECE; Regional University of Cariri—URCA Format- basic alumina as solid support. J Chilean Chem Soc 63(2):3983–
ting of funding sources. Fundacąõ Cearense de Apoio ao Desen- 3987. https://​doi.​org/​10.​4067/​s0717-​97072​01800​02039​83
volvimento Cientı´fico e Tecnolo´ gico—FUNCAP; Coordenacąõ de Assef APDC, Neto OCC (2020) Bases moleculares da resistência bac-
Aperfeic¸oamento de Pessoal de Nı´vel Superior—CAPES; Conselho teriana. In: Brasil, Agência Nacional de Vigilância Sanitária.
Nacional de Desenvolvimento Cientı´fico e Tecnoloógico—CNPq. Microbiologia Clínica Para O Controle De Infecção Relacionada
à Assistência á Saúde, 1° edn. Brasília, Anvisa, pp. 17–28
Data availability All data will be available after a reasonable request Babu AK, Selvaraju K (2020) Synthesis, biological evaluation and
to the corresponding author. docking studies of novel chalcone derivatives as antimicrobial
agents. Mater Today Proc 48(xxxx):382–386
Declarations Babu K, Selvi D, Pitchai D (2015) Synthesis and microbial studies of
novel 1, 3-thiazine compounds bearing schiff base moiety. Der
Conflict of interest The authors declare that they have no known con- Pharma Chemica 7(10):89–92
flict of interest to disclose. Banoth RK, Thatikonda A (2020) A review on natural chalcones: an
update. Int J Pharm Sci Res 11:546–555
Ethical statements This article is according with to the international, Barroso H, Meliço-Silvestre A, Taveira N (2014) Microbiologia
national and institutional rules considering biodiversity rights. médica: fundamentos de microbiologia, conceito básicos da res-
posta imunológica, princípios do diagnóstico, microbiológico
médico e bacteriologia. (LIDEL - Edições Técnicas Lda, Ed.).
Lisboa
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