Login Register Cart 0
Generic placeholder image

Current Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Review Article

Chalcone Derivatives as Antibacterial Agents: An Updated Overview

Author(s): Aldo S. de Oliveira*, Arthur R. Cenci, Lucas Gonçalves, Maria Eduarda C. Thedy, Angelica Justino, Antônio L. Braga and Lidiane Meier

Volume 31, Issue 17, 2024

Published on: 04 April, 2023

Page: [2314 - 2329] Pages: 16

DOI: 10.2174/0929867330666230220140819

Price: $65

Abstract

Background: The indiscriminate use of antibiotics brings an alarming reality: in 2050, bacterial resistance could be the main cause of death in the world, resulting in the death of 10 million people, according to the World Health Organization (WHO). In this sense, to combat bacterial resistance, several natural substances, including chalcones, have been described in relation to antibacterial, representing a potential tool for the discovery of new antibacterial drugs.

Objective: The objective of this study is to perform a bibliographic survey and discuss the main contributions in the literature about the antibacterial potential of chalcones in the last 5 years.

Methods: A search was carried out in the main repositories, for which the publications of the last 5 years were investigated and discussed. Unprecedented in this review, in addition to the bibliographic survey, molecular docking studies were carried out to exemplify the applicability of using one of the molecular targets for the design of new entities with antibacterial activity.

Results: In the last 5 years, antibacterial activities were reported for several types of chalcones, for which activities were observed for both gram-positive and gram-negative bacteria with high potency, including MIC values in the nanomolar range. Molecular docking simulations demonstrated important intermolecular interactions between chalcones and residues from the enzymatic cavity of the enzyme DNA gyrase, one of the validated molecular targets in the development of new antibacterial agents.

Conclusion: The data presented demonstrate the potential of using chalcones in drug development programs with antibacterial properties, which may be useful to combat resistance, a worldwide public health problem.

« Previous Next »
[1]
Leonard, A.F.C.; Morris, D.; Schmitt, H.; Gaze, W.H. Natural recreational waters and the risk that exposure to antibiotic resistant bacteria poses to human health. Curr. Opin. Microbiol., 2022, 65, 40-46.
[http://dx.doi.org/10.1016/j.mib.2021.10.004] [PMID: 34739925]
[2]
Yadav, M. Potential prospective to counter antibiotic-resistant pathogens; Comprehensive Gut Microbiota, 2022. [Epub ahead of print
[3]
Ahamed, M.J.N.; Ibrahim, F.B.; Srinivasan, H. Synergistic interactions of antimicrobials to counteract the drug-resistant microorganisms. Biointerface Res. Appl. Chem., 2022, 12, 861-872.
[http://dx.doi.org/10.33263/briac121.861872]
[4]
Luz, C.F.; van Niekerk, J.M.; Keizer, J.; Beerlage-de Jong, N.; Braakman-Jansen, L.M.A.; Stein, A.; Sinha, B.; van Gemert-Pijnen, J.E.W.C.; Glasner, C. Mapping twenty years of antimicrobial resistance research trends. Artif. Intell. Med., 2022, 123, 102216.
[http://dx.doi.org/10.1016/j.artmed.2021.102216] [PMID: 34998519]
[5]
Moretto, V.T.; Bartley, P.S.; Ferreira, V.M.; Santos, C.S.; Silva, L.K.; Ponce-Terashima, R.A.; Blanton, R.E.; Reis, M.G.; Barbosa, L.M. Microbial source tracking and antimicrobial resistance in one river system of a rural community in Bahia, Brazil. Braz. J. Biol., 2021, 82, e231838.
[http://dx.doi.org/10.1590/1519-6984.231838] [PMID: 33681894]
[6]
Rizvi, S.G.; Ahammad, S.Z. COVID-19 and antimicrobial resistance: A cross-study. Sci. Total Environ., 2022, 807(Pt 2), 150873.
[http://dx.doi.org/10.1016/j.scitotenv.2021.150873] [PMID: 34634340]
[7]
Amarsy, R.; Trystram, D.; Cambau, E.; Monteil, C.; Fournier, S.; Oliary, J.; Junot, H.; Sabatier, P.; Porcher, R.; Robert, J.; Jarlier, V.; Arlet, G.; Lefevre, L.A.; Aubry, A.; Belec, L.; Bercot, B.; Bonacorsi, S.; Calvez, V.; Cambau, E.; Carbonnelle, E.; Chevaliez, S.; Decousser, J-W.; Delaugerre, C.; Descamps, D.; Doucet-Populaire, F.; Gaillard, J-L.; Chenon, A.G. Surging bloodstream infections and antimicrobial resistance during the first wave of COVID-19: A study in a large multihospital institution in the Paris region. Int. J. Infect. Dis., 2022, 114, 90-96.
[http://dx.doi.org/10.1016/j.ijid.2021.10.034] [PMID: 34688945]
[8]
Costa, A.; Junior, A. Bacterial resistance to antibiotics and public health: A brief literature review. Sci. Station, 2017, 7, 45.
[http://dx.doi.org/10.18468/estcien.2017v7n2.p45-57]
[9]
WHO Regional Office for Europe. Preventing the COVID-19 Pandemic from Causing an Antibiotic Resistance Catastrophe., 2020. Available from: https://www.who.int/europe/news/item/18-11-2020-preventing-the-covid-19-pandemic-from-causing-an-antibiotic-resistance-catastrophe
[10]
Wei, W.; Ortwine, J.K.; Mang, N.S.; Joseph, C.; Hall, B.C.; Prokesch, B.C. Limited role for antibiotics in COVID-19: Scarce evidence of bacterial coinfection. medRxiv, 2020.
[11]
Cohen, F.L.; Tartasky, D. Microbial resistance to drug therapy: A review. Am. J. Infect. Control, 1997, 25(1), 51-64.
[http://dx.doi.org/10.1016/s0196-6553(97)90054-7] [PMID: 9057945]
[12]
Sulis, G.; Sayood, S.; Gandra, S. Antimicrobial resistance in low- and middle-income countries: Current status and future directions. Expert Rev. Anti Infect. Ther., 2022, 20(2), 147-160.
[http://dx.doi.org/10.1080/14787210.2021.1951705] [PMID: 34225545]
[13]
Murray, C.J.L.; Ikuta, K.S.; Sharara, F.; Swetschinski, L.; Robles Aguilar, G.; Gray, A.; Han, C.; Bisignano, C.; Rao, P.; Wool, E.; Johnson, S.C.; Browne, A.J.; Chipeta, M.G.; Fell, F.; Hackett, S.; Haines-Woodhouse, G.; Kashef Hamadani, B.H.; Kumaran, E.A.P.; McManigal, B.; Agarwal, R.; Akech, S.; Albertson, S.; Amuasi, J.; Andrews, J.; Aravkin, A.; Ashley, E.; Bailey, F.; Baker, S.; Basnyat, B.; Bekker, A.; Bender, R.; Bethou, A.; Bielicki, J.; Boonkasidecha, S.; Bukosia, J.; Carvalheiro, C.; Castañeda-Orjuela, C.; Chansamouth, V.; Chaurasia, S.; Chiurchiù, S.; Chowdhury, F.; Cook, A.J.; Cooper, B.; Cressey, T.R.; Criollo-Mora, E.; Cunningham, M.; Darboe, S.; Day, N.P.J.; De Luca, M.; Dokova, K.; Dramowski, A.; Dunachie, S.J.; Eckmanns, T.; Eibach, D.; Emami, A.; Feasey, N.; Fisher-Pearson, N.; Forrest, K.; Garrett, D.; Gastmeier, P.; Giref, A.Z.; Greer, R.C.; Gupta, V.; Haller, S.; Haselbeck, A.; Hay, S.I.; Holm, M.; Hopkins, S.; Iregbu, K.C.; Jacobs, J.; Jarovsky, D.; Javanmardi, F.; Khorana, M.; Kissoon, N.; Kobeissi, E.; Kostyanev, T.; Krapp, F.; Krumkamp, R.; Kumar, A.; Kyu, H.H.; Lim, C.; Limmathurotsakul, D.; Loftus, M.J.; Lunn, M.; Ma, J.; Mturi, N.; Munera-Huertas, T.; Musicha, P.; Mussi-Pinhata, M.M.; Nakamura, T.; Nanavati, R.; Nangia, S.; Newton, P.; Ngoun, C.; Novotney, A.; Nwakanma, D.; Obiero, C.W.; Olivas-Martinez, A.; Olliaro, P.; Ooko, E.; Ortiz-Brizuela, E.; Peleg, A.Y.; Perrone, C.; Plakkal, N.; Ponce-de-Leon, A.; Raad, M.; Ramdin, T.; Riddell, A.; Roberts, T.; Robotham, J.V.; Roca, A.; Rudd, K.E.; Russell, N.; Schnall, J.; Scott, J.A.G.; Shivamallappa, M.; Sifuentes-Osornio, J.; Steenkeste, N.; Stewardson, A.J.; Stoeva, T.; Tasak, N.; Thaiprakong, A.; Thwaites, G.; Turner, C.; Turner, P.; van Doorn, H.R.; Velaphi, S.; Vongpradith, A.; Vu, H.; Walsh, T.; Waner, S.; Wangrangsimakul, T.; Wozniak, T.; Zheng, P.; Sartorius, B.; Lopez, A.D.; Stergachis, A.; Moore, C.; Dolecek, C.; Naghavi, M. Global burden of bacterial antimicrobial resistance in 2019: A systematic analysis. Lancet, 2022, 399(10325), 629-655.
[http://dx.doi.org/10.1016/S0140-6736(21)02724-0] [PMID: 35065702]
[14]
Mustikasari, K.; Santoso, U.T. The benefits of chalcone and its derivatives as antibacterial agents: A review. BIO Web. Conf., 2020, 20, p. 03007.
[15]
Shah, P.; Westwell, A.D. The role of fluorine in medicinal chemistry. J. Enzyme Inhib. Med. Chem., 2007, 22(5), 527-540.
[http://dx.doi.org/10.1080/14756360701425014] [PMID: 18035820]
[16]
Burmaoglu, S.; Algul, O.; Gobek, A.; Aktas Anil, D.; Ulger, M.; Erturk, B.G.; Kaplan, E.; Dogen, A.; Aslan, G. Design of potent fluoro-substituted chalcones as antimicrobial agents. J. Enzyme Inhib. Med. Chem., 2017, 32(1), 490-495.
[http://dx.doi.org/10.1080/14756366.2016.1265517] [PMID: 28118738]
[17]
Chu, W-C.; Bai, P-Y.; Yang, Z-Q.; Cui, D-Y.; Hua, Y-G.; Yang, Y.; Yang, Q-Q.; Zhang, E.; Qin, S. Synthesis and antibacterial evaluation of novel cationic chalcone derivatives possessing broad spectrum antibacterial activity. Eur. J. Med. Chem., 2018, 143, 905-921.
[http://dx.doi.org/10.1016/j.ejmech.2017.12.009] [PMID: 29227931]
[18]
Zhang, M.; Prior, A.M.; Maddox, M.M.; Shen, W-J.; Hevener, K.E.; Bruhn, D.F.; Lee, R.B.; Singh, A.P.; Reinicke, J.; Simmons, C.J.; Hurdle, J.G.; Lee, R.E.; Sun, D. Pharmacophore modeling, synthesis, and antibacterial evaluation of chalcones and derivatives. ACS Omega, 2018, 3(12), 18343-18360.
[http://dx.doi.org/10.1021/acsomega.8b03174] [PMID: 30613820]
[19]
Prakash, G.; Boopathy, M.; Selvam, R.; Johnsanthosh Kumar, S.; Subramanian, K. The effect of anthracene-based chalcone derivatives in the resazurin dye reduction assay mechanisms for the investigation of gram-positive and gram-negative bacterial and fungal infection. New J. Chem., 2018, 42, 1037-1045.
[http://dx.doi.org/10.1039/C7NJ04125J]
[20]
Meier, D.; Hernández, M.V.; van Geelen, L.; Muharini, R.; Proksch, P.; Bandow, J.E.; Kalscheuer, R. The plant-derived chalcone Xanthoangelol targets the membrane of Gram-positive bacteria. Bioorg. Med. Chem., 2019, 27(23), 115151.
[http://dx.doi.org/10.1016/j.bmc.2019.115151] [PMID: 31648878]
[21]
Jin, H.; Jiang, X.; Yoo, H.; Wang, T.; Sung, C.G.; Choi, U.; Lee, C-R.; Yu, H.; Koo, S. Synthesis of chalcone-derived heteroaromatics with antibacterial activities. ChemistrySelect, 2020, 5, 12421-12424.
[http://dx.doi.org/10.1002/slct.202003397]
[22]
Mustafa, M.; Mostafa, Y.A. A facile synthesis, drug-likeness, and in silico molecular docking of certain new azidosulfonamide–chalcones and their in vitro antimicrobial activity. Monatshefte Chem., 2020, 151, 417-427.
[http://dx.doi.org/10.1007/s00706-020-02568-8]
[23]
Narwal, S.; Kumar, S.; Verma, P.K. Synthesis and biological activity of new chalcone scaffolds as prospective antimicrobial agents. Res. Chem. Intermed., 2021, 47, 1625-1641.
[http://dx.doi.org/10.1007/s11164-020-04359-6]
[24]
Hu, Y.; Hu, C.; Pan, G.; Yu, C.; Ansari, M.F.; Yadav Bheemanaboina, R.R.; Cheng, Y.; Zhou, C.; Zhang, J. Novel chalcone-conjugated, multi-flexible end-group coumarin thiazole hybrids as potential antibacterial repressors against methicillin-resistant Staphylococcus aureus. Eur. J. Med. Chem., 2021, 222, 113628.
[http://dx.doi.org/10.1016/j.ejmech.2021.113628] [PMID: 34139627]
[25]
Yadav, M.; Lal, K.; Kumar, A.; Kumar, A.; Kumar, D. Indole-chalcone linked 1,2,3-triazole hybrids: Facile synthesis, antimicrobial evaluation and docking studies as potential antimicrobial agents. J. Mol. Struct., 2022, 1261, 132867.
[http://dx.doi.org/10.1016/j.molstruc.2022.132867]
[26]
Silver, L.L. Appropriate targets for antibacterial drugs. Cold Spring Harb. Perspect. Med., 2016, 6(12), 1-7.
[http://dx.doi.org/10.1101/cshperspect.a030239] [PMID: 27599531]
[27]
Christensen, D.J.; Gottlin, E.B.; Benson, R.E.; Hamilton, P.T. Phage display for target-based antibacterial drug discovery. Drug Discov. Today, 2001, 6(14), 721-727.
[http://dx.doi.org/10.1016/s1359-6446(01)01853-0] [PMID: 11445463]
[28]
Baron, S. Medical Microbiology, 4th ed; Univ of Texas Medical Branch: USA, 1996.
[29]
Silhavy, T.J.; Kahne, D.; Walker, S. The bacterial cell envelope. Cold Spring Harb. Perspect. Biol., 2010, 2(5), a000414.
[http://dx.doi.org/10.1101/cshperspect.a000414] [PMID: 20452953]
[30]
Uzman, A. Molecular Biology of the Cell 4th Ed.: Alberts, B., Johnson, A., Lewis, J., Raff, M., Roberts, K., and Walter, P. Biochem. Mol. Biol. Educ., 2003, 31, 212-214.
[31]
Zgurskaya, H.I.; Löpez, C.A.; Gnanakaran, S. Permeability barrier of gram-negative cell envelopes and approaches to bypass it. ACS Infect. Dis., 2015, 1(11), 512-522.
[http://dx.doi.org/10.1021/acsinfecdis.5b00097] [PMID: 26925460]
[32]
Bush, K. Bradford, P.A. β-lactams and β-lactamase inhibitors: An overview. Cold Spring Harb. Perspect. Med., 2016, 6(8), a025247.
[http://dx.doi.org/10.1101/cshperspect.a025247] [PMID: 27329032]
[33]
Tahlan, K.; Jensen, S.E. Origins of the β-lactam rings in natural products. J. Antibiot., 2013, 66(7), 401-410.
[http://dx.doi.org/10.1038/ja.2013.24] [PMID: 23531986]
[34]
Chukwudi, C.U. rRNA binding sites and the molecular mechanism of action of the tetracyclines. Antimicrob. Agents Chemother., 2016, 60(8), 4433-4441.
[35]
Chellat, M.F.; Raguž, L.; Riedl, R. Targeting antibiotic resistance. Angew. Chem. Int. Ed. Engl., 2016, 55(23), 6600-6626.
[http://dx.doi.org/10.1002/anie.201506818] [PMID: 27000559]
[36]
Drlica, K.; Hiasa, H.; Kerns, R.; Malik, M.; Mustaev, A.; Zhao, X. Quinolones: Action and resistance updated. Curr. Top. Med. Chem., 2009, 9(11), 981-998.
[http://dx.doi.org/10.2174/156802609789630947] [PMID: 19747119]
[37]
Aldred, K.J.; Kerns, R.J.; Osheroff, N. Mechanism of quinolone action and resistance. Biochemistry, 2014, 53(10), 1565-1574.
[http://dx.doi.org/10.1021/bi5000564] [PMID: 24576155]
[38]
Hooper, D.C.; Jacoby, G.A. Topoisomerase inhibitors: Fluoroquinolone mechanisms of action and resistance. Cold Spring Harb. Perspect. Med., 2016, 6(9), 1-21.
[http://dx.doi.org/10.1101/cshperspect.a025320] [PMID: 27449972]
[39]
Poirel, L.; Jayol, A.; Nordmann, P. Polymyxins: Antibacterial activity, susceptibility testing, and resistance mechanisms encoded by plasmids or chromosomes. Clin. Microbiol. Rev., 2017, 30(2), 557-596.
[http://dx.doi.org/10.1128/CMR.00064-16] [PMID: 28275006]
[40]
Kołton, A.; Długosz-Grochowska, O.; Wojciechowska, R.; Czaja, M. Biosynthesis regulation of folates and phenols in plants. Sci. Hortic., 2022, 291, 110561.
[41]
Wallace-Povirk, A.; Tong, N.; Wong-Roushar, J.; O’Connor, C.; Zhou, X.; Hou, Z.; Bao, X.; Garcia, G.E.; Li, J.; Kim, S.; Dann, C.E.; Matherly, L.H.; Gangjee, A. Discovery of 6-substituted thieno[2,3-d]pyrimidine analogs as dual inhibitors of glycinamide ribonucleotide formyltransferase and 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase in de novo purine nucleotide biosynthesis in folate receptor expressing human tumors. Bioorg. Med. Chem., 2021, 37, 116093.
[42]
Feng, G.; Zou, W.; Zhong, Y. Sulfonamides repress cell division in the root apical meristem by inhibiting folates synthesis. J. Hazard. Mater. Adv., 2022, 5, 100045.
[http://dx.doi.org/10.1016/j.hazadv.2022.100045]
[43]
Yang, H.; Zhang, X.; Liu, Y.; Liu, L.; Li, J.; Du, G.; Chen, J. Synthetic biology-driven microbial production of folates: Advances and perspectives. Bioresour. Technol., 2021, 324, 124624.
[44]
The Biochemistry of Folic Acid and Related Pteridines; North-Holland Publishing Company, 1969.
[45]
Lin, S.; Chen, Y.; Li, H.; Liu, J.; Liu, S. Design, synthesis, and evaluation of amphiphilic sofalcone derivatives as potent Gram-positive antibacterial agents. Eur. J. Med. Chem., 2020, 202, 112596.
[http://dx.doi.org/10.1016/j.ejmech.2020.112596] [PMID: 32659547]
[46]
Jones, G.; Willett, P.; Glen, R.C.; Leach, A.R.; Taylor, R. Development and validation of a genetic algorithm for flexible docking. J. Mol. Biol., 1997, 267(3), 727-748.
[http://dx.doi.org/10.1006/jmbi.1996.0897] [PMID: 9126849]
[47]
Korb, O.; Stützle, T.; Exner, T.E. Empirical scoring functions for advanced protein-ligand docking with PLANTS. J. Chem. Inf. Model., 2009, 49(1), 84-96.
[http://dx.doi.org/10.1021/ci800298z] [PMID: 19125657]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy