Synthesis and Evaluation of Selected Benzimidazole Derivatives As Potential Antimicrobial Agents

Overview

Journal Molecules

Publisher MDPI

Specialty Biology

Date 2015 Aug 27

PMID 26307956

Citations 20

Authors

Fatmah A S Alasmary

Anna M Snelling

Mohammed E Zain

Ahmed M Alafeefy

Amani S Awaad

Nazira Karodia

Affiliations

Soon will be listed here.

Abstract

A library of 53 benzimidazole derivatives, with substituents at positions 1, 2 and 5, were synthesized and screened against a series of reference strains of bacteria and fungi of medical relevance. The SAR analyses of the most promising results showed that the antimicrobial activity of the compounds depended on the substituents attached to the bicyclic heterocycle. In particular, some compounds displayed antibacterial activity against two methicillin-resistant Staphylococcus aureus (MRSA) strains with minimum inhibitory concentrations (MICs) comparable to the widely-used drug ciprofloxacin. The compounds have some common features; three possess 5-halo substituents; two are derivatives of (S)-2-ethanaminebenzimidazole; and the others are derivatives of one 2-(chloromethyl)-1H-benzo[d]imidazole and (1H-benzo[d]imidazol-2-yl)methanethiol. The results from the antifungal screening were also very interesting: 23 compounds exhibited potent fungicidal activity against the selected fungal strains. They displayed equivalent or greater potency in their MIC values than amphotericin B. The 5-halobenzimidazole derivatives could be considered promising broad-spectrum antimicrobial candidates that deserve further study for potential therapeutic applications.

Citing Articles

Design, Synthesis, and Anti-Melanogenic Activity of 2-Mercaptomethylbenzo[]imidazole Derivatives Serving as Tyrosinase Inhibitors: An In Silico, In Vitro, and In Vivo Exploration.

Jin Jung H, Park H, Kim H, Soo Park H, Park Y, Chun P Antioxidants (Basel). 2024; 13(10).

PMID: 39456501 PMC: 11505594. DOI: 10.3390/antiox13101248.

Approaches for Exploring the Pharmacological Activities of Benzimidazole Derivatives: A Comprehensive Review.

Srivastava M, Singh K, Kumar S, Hasan S, Mujeeb S, Kushwaha S Mini Rev Med Chem. 2024; 24(16):1481-1495.

PMID: 38288816 DOI: 10.2174/0113895575287322240115115125.

Efficient synthesis of 1,2-disubstituted benzimidazoles catalyzed by phosphoric acid as a homogeneous catalyst under mild conditions and investigating their anti-diabetes properties through molecular docking studies and calculations.

Moazeni Bistgani A, Dehghani A, Moradi L RSC Adv. 2023; 13(51):35781-35790.

PMID: 38074406 PMC: 10706800. DOI: 10.1039/d3ra07156a.

A Critical Review on Therapeutic Potential of Benzimidazole Derivatives: A Privileged Scaffold.

Natarajan R, Kumar P, Subramani A, Siraperuman A, Angamuthu P, Bhandare R Med Chem. 2023; 20(3):311-351.

PMID: 37946342 DOI: 10.2174/0115734064253813231025093707.

Synthesis, antimicrobial activity and molecular docking study of benzyl functionalized benzimidazole silver(I) complexes.

Ari E, Sahin N, Ustun E, Dundar M, Karci H, Ozdemir I J Biol Inorg Chem. 2023; 28(8):725-736.

PMID: 37934281 DOI: 10.1007/s00775-023-02024-y.

References

Soderlind K, Gorodetsky B, Singh A, Bachur N, Miller G, Lown J . Bis-benzimidazole anticancer agents: targeting human tumour helicases. Anticancer Drug Des. 1999; 14(1):19-36. View

Stefanska J, Gralewska R, Starosciak B, Kazimierczuk Z . Antimicrobial activity of substituted azoles and their nucleosides. Pharmazie. 2000; 54(12):879-84. View

Valdez J, Cedillo R, Hernandez-Campos A, Yepez L, Hernandez-Luis F, Navarrete-Vazquez G . Synthesis and antiparasitic activity of 1H-benzimidazole derivatives. Bioorg Med Chem Lett. 2002; 12(16):2221-4. DOI: 10.1016/s0960-894x(02)00346-3. View

Barrett C, Barrett J . Antibacterials: are the new entries enough to deal with the emerging resistance problems?. Curr Opin Biotechnol. 2003; 14(6):621-6. DOI: 10.1016/j.copbio.2003.10.003. View

Velik J, Baliharova V, Fink-Gremmels J, Bull S, Lamka J, Skalova L . Benzimidazole drugs and modulation of biotransformation enzymes. Res Vet Sci. 2003; 76(2):95-108. DOI: 10.1016/j.rvsc.2003.08.005. View

Tonelli M, Paglietti G, Boido V, Sparatore F, Marongiu F, Marongiu E . Antiviral activity of benzimidazole derivatives. I. Antiviral activity of 1-substituted-2-[(benzotriazol-1/2-yl)methyl]benzimidazoles. Chem Biodivers. 2008; 5(11):2386-401. DOI: 10.1002/cbdv.200890203. View

Shingalapur R, Hosamani K, Keri R, Hugar M . Derivatives of benzimidazole pharmacophore: synthesis, anticonvulsant, antidiabetic and DNA cleavage studies. Eur J Med Chem. 2010; 45(5):1753-9. DOI: 10.1016/j.ejmech.2010.01.007. View

Achar K, Hosamani K, Seetharamareddy H . In-vivo analgesic and anti-inflammatory activities of newly synthesized benzimidazole derivatives. Eur J Med Chem. 2010; 45(5):2048-54. DOI: 10.1016/j.ejmech.2010.01.029. View

Tonelli M, Simone M, Tasso B, Novelli F, Boido V, Sparatore F . Antiviral activity of benzimidazole derivatives. II. Antiviral activity of 2-phenylbenzimidazole derivatives. Bioorg Med Chem. 2010; 18(8):2937-53. DOI: 10.1016/j.bmc.2010.02.037. View

10.

Vitale G, Corona P, Loriga M, Carta A, Paglietti G, Ibba C . Styrylbenzimidazoles. Synthesis and biological activity - part 3. Med Chem. 2010; 6(2):70-8. DOI: 10.2174/157340610791321514. View

11.

Gonzalez-Chavez M, Mendez F, Martinez R, Perez-Gonzalez C, Martinez-Gutierrez F . Design and synthesis of anti-MRSA benzimidazolylbenzene-sulfonamides. QSAR studies for prediction of antibacterial activity. Molecules. 2010; 16(1):175-89. PMC: 6259222. DOI: 10.3390/molecules16010175. View

12.

Siddiqui N, Andalip , Bawa S, Ali R, Afzal O, Akhtar M . Antidepressant potential of nitrogen-containing heterocyclic moieties: An updated review. J Pharm Bioallied Sci. 2011; 3(2):194-212. PMC: 3103913. DOI: 10.4103/0975-7406.80765. View

13.

Franco B, Altagracia Martinez M, Sanchez Rodriguez M, Wertheimer A . The determinants of the antibiotic resistance process. Infect Drug Resist. 2011; 2:1-11. PMC: 3108730. View

14.

Vitale G, Corona P, Loriga M, Carta A, Paglietti G, Giliberti G . 5-acetyl-2-arylbenzimidazoles as antiviral agents. Part 4. Eur J Med Chem. 2012; 53:83-97. DOI: 10.1016/j.ejmech.2012.03.038. View

15.

Bansal Y, Silakari O . The therapeutic journey of benzimidazoles: a review. Bioorg Med Chem. 2012; 20(21):6208-36. DOI: 10.1016/j.bmc.2012.09.013. View

16.

Mentese E, Bektas H, Ulker S, Bekircan O, Kahveci B . Microwave-assisted synthesis of new benzimidazole derivatives with lipase inhibition activity. J Enzyme Inhib Med Chem. 2013; 29(1):64-8. DOI: 10.3109/14756366.2012.753880. View

17.

Imperi F, Massai F, Facchini M, Frangipani E, Visaggio D, Leoni L . Repurposing the antimycotic drug flucytosine for suppression of Pseudomonas aeruginosa pathogenicity. Proc Natl Acad Sci U S A. 2013; 110(18):7458-63. PMC: 3645532. DOI: 10.1073/pnas.1222706110. View

18.

Kumar K, Awasthi D, Lee S, Cummings J, Knudson S, Slayden R . Benzimidazole-based antibacterial agents against Francisella tularensis. Bioorg Med Chem. 2013; 21(11):3318-26. PMC: 3681959. DOI: 10.1016/j.bmc.2013.02.059. View

19.

Ke Y, Zhi X, Yu X, Ding G, Yang C, Xu H . Combinatorial synthesis of benzimidazole-azo-phenol derivatives as antifungal agents. Comb Chem High Throughput Screen. 2013; 17(1):89-95. DOI: 10.2174/13862073113166660058. View

20.

Cole S . Who will develop new antibacterial agents?. Philos Trans R Soc Lond B Biol Sci. 2014; 369(1645):20130430. PMC: 4024223. DOI: 10.1098/rstb.2013.0430. View