* Corresponding Author
Facile Synthesis, Characterization and in vitro Antibacterial Efficacy of Functionalized 2-Substituted Benzimidazole Motifs
https://doi.org/10.22146/ijc.40448 Olayinka Oyewale Ajani(1*), Olaoluwasubomi Eneyeme Joseph(2), King Tamunodikibugerere Iyaye(3), Natasha October(4), Damilola Victoria Aderohunmu(5), Shade John Olorunshola(6), Oluwatosin Yemisi Audu(7)
(1) Department of Chemistry, College of Science and Technology, Covenant University, Canaanland, Km 10 Idiroko Road, P.M.B. 1023, Ota, Ogun State, Nigeria
(2) Department of Chemistry, College of Science and Technology, Covenant University, Canaanland, Km 10 Idiroko Road, P.M.B. 1023, Ota, Ogun State, Nigeria
(3) Department of Chemistry, College of Science and Technology, Covenant University, Canaanland, Km 10 Idiroko Road, P.M.B. 1023, Ota, Ogun State, Nigeria
(4) Department of Chemistry, University of Pretoria, Lynnwood Road, Hatfield, Pretoria, 0002, South Africa
(5) Department of Chemistry, College of Science and Technology, Covenant University, Canaanland, Km 10 Idiroko Road, P.M.B. 1023, Ota, Ogun State, Nigeria
(6) Department of Biological Science, College of Science and Technology, Covenant University, Canaanland, Km 10 Idiroko Road, P.M.B. 1023, Ota, Ogun State, Nigeria
(7) Department of Chemistry, University of Pretoria, Lynnwood Road, Hatfield, Pretoria, 0002, South Africa
(*) Corresponding Author
Abstract
A series of functionalized 2-substituted benzimidazole motifs was designed and successfully synthesized via thermal cyclization of 1,2-diaminobenzene on COOH end of L- leucine to achieve benzimidazole derivatives 6 as the essential precursor. The coupling of the precursor 6 with benzaldehyde derivatives a-h, ketone series i-k, and aryl sulfonyl chlorides l-n led to the formation of the targeted 2-substituted benzimidazole motifs 7a-n in improved yields. The targeted benzimidazole motifs were structurally authenticated through their spectral data and microanalytical parameters. The targeted final moieties were investigated for potential antimicrobial activity using the agar diffusion method with gentamicin as the clinical standard. All the compounds had a broad spectrum of activity with compound 7k having the highest remarkable activity with MIC of 0.98 ± 0.02 µg/mL and MBC value of 3.91 ± 0.10 µg/mL. These findings suggest that compound 7k containing camphor might be a good candidate for the design of new antimicrobial small-molecule drugs.
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References
[1] Polshettiwar, V., and Varma, R. S., 2008, Greener and expeditious synthesis of bioactive heterocycles using microwave irradiation, Pure Appl. Chem., 80 (4), 777–790.
[2] Ajani, O.O., Aderohunmu, D.V., Ikpo, C.O., Adedapo, A.E., and Olanrewaju, I.O., 2016, Functionalized benzimidazole scaffolds: Privileged heterocycle for drug design in therapeutic medicine, Arch. Pharm., 349 (7), 475–506.
[3] Srivastava, S., Pandeya, S.N., Yadav, M.K., and Singh, B.K., 2013, Synthesis and analgesic activity of novel derivatives of 1,2-substituted benzimidazoles, J. Chem., 2013, 694295.
[4] Salahuddin, Salahuddin, Shaharyar, M., and Mazumder, A., 2017, Benzimidazoles: A biologically active compounds, Arabian J. Chem., 10 (Suppl. 1), S157–S173.
[5] Alaqeel, S.I., 2017, Synthetic approaches to benzimidazoles from o-phenylenediamine: A literature review, J. Saudi Chem. Soc., 21 (2), 229–237.
[6] Ajani, O.O., Ezeoke, E.K., Edobor-Osoh, A., and Ajani, A.O., 2013, Facile synthesis and characterization of new 2,3-disubstituted benzimidazole derivatives, Int. Res. J. Pure Appl. Chem., 3 (1), 10–21.
[7] Rithe, S.R., Jagtap, R.S., and Ubarhande, S.S., 2015, One pot synthesis of substituted benzimidazole derivatives and their characterization, Rasayan J. Chem., 8 (2), 213–217.
[8] Patil, S.A., Patil, S.A., and Patil, R., 2017, Medicinal applications of (benz)imidazole- and indole-based macrocycles, Chem. Biol. Drug Des., 89 (4), 639–649.
[9] Maruthamuthu, Rajam, S., Stella, P.C.R., Dileepan, A.G.B., and Ranjith, R., 2016, The chemistry and biological significance of imidazole, benzimidazole, benzoxazole, tetrazole and quinazolinone nucleus, J. Chem. Pharm. Res., 8 (5), 505–526.
[10] Chang, Y.S., 2012, Hypersensitivity reactions to proton pump inhibitors, Curr. Opin. Allergy Clin. Immunol., 12 (4), 348–353.
[11] Ali, M.S., Saeed, K., Rashid, I., Ijaz, M., Akbar, H., Rashid, M., and Ashraf, K., 2018, Anthelmintic drugs: Their efficacy and cost-effectiveness in different parity cattle, J. Parasitol., 104 (1), 79–85.
[12] Iwamoto, K., Uehara, Y., Inoue, Y., Taguchi, K., Muraoka, D., Ogo, N., Matsuno, K., and Asai, A., 2017, Inhibition of STAT3 by anticancer drug bendamustine, PLoS One, 12 (1), 1–18.
[13] Zhang, P., Wang, H., Sun, L., Zhang, J., Xi, Y., Wu, Y., Yan, L.L., Li, X., and Sun, N., 2017, Telmisartan and hydrochlorothiazide antihypertensive treatment in high sodium intake population: A randomized double-blind trial, J. Hypertens., 35 (10), 2077–2085.
[14] Lieberman, L.A., and Higgins, D.E., 2009, A small-molecule screen identifies the antipsychotic drug pimozide as an inhibitor of Listeria monocytogenes infection, Antimicrob. Agents Chemother., 53 (2), 756–764.
[15] Farahat, A.A., Ismail, M.A., Kumar, A., Wenzler, T., Brun, R., Paul, A., Wilson, W.D., and Boykin, D.W., 2018, Indole and benzimidazole bichalcophenes: Synthesis, DNA binding and antiparasitic activity, Eur. J. Med. Chem., 143, 1590–1596.
[16] Anand, K., and Wakode, S., 2018, Synthesis, characterization and biological evaluation of benzimidazole derivatives, Int. J. Pharm. Sci. Res., 9 (2), 617–624.
[17] Kadhim, A.J., and Kazim, A.C., 2018, Synthesis and characterization of benzimidazole by using O-phenylenediamine with different aldehydes and carboxylic acids in the presence of ρ-tsOh as a catalyst, Orient. J. Chem., 34 (4), 2131–2136.
[18] Çevik, U.A., Nurpelin, S.B., Mina, A.C., Yusuf, Ö., and Özlem, A., 2018, Synthesis and evaluation of new benzimidazole derivatives with hydrazone moiety as anticancer agents, Turk. J. Biochem., 43 (2), 151–158.
[19] Gupta, P.D., and Birdi, T.J., 2017, Development of botanicals to combat antibiotic resistance, J. Ayurveda Integr. Med., 8 (4), 266–275.
[20] Ajani, O.O., Tolu-Bolaji, O.O., Olorunshola, S.J., Zhao, Y., and Aderohunmu, D.V., 2017, Structure-based design of functionalized 2-substituted and 1,2-disubstituted benzimidazole derivatives and their in vitro antibacterial efficacy, J. Adv. Res., 8 (6), 703–712.
[21] Ajani, O.O., Obafemi, C.A., Nwinyi, O.C., and Akinpelu, D.A., 2010, Microwave assisted synthesis and antimicrobial activity of 2-quinoxalinone-3-hydrazone derivatives, Bioorg. Med. Chem., 18 (1), 214–221.
[22] Komurcu, S.G., Rollas, S., Ulgen, M., Gorrod, J.W., and Cevikbas, A., 1995, Evaluation of some arylhydrazones of p-aminobenzoic acid hydrazide as antimicrobial agents and their in vitro hepatic microsomal metabolism, Boll. Chim. Farm., 135 (7), 375–379.
[23] Prescott, L.M., Harley, J.P., and Klein, D.A., 2005, Microbiology, 6th Ed., McGraw-Hill, Inc., New York.
[24] Bottone, E.J., 2010, Bacillus cereus, a volatile human pathogen, Clin. Microbiol. Rev., 23 (2), 382–398.
[25] Arhin, A., and Boucher, C., 2010, The outer membrane protein OprQ and adherence of Pseudomonas aeruginosa to human fibronectin, Microbiology, 156 (5), 1415–1423.
[26] Ren, Y., Zhang, L., Zhou, C.H., and Geng, R.X., 2014, Recent development of benzotriazole-based medicinal drugs, Med. Chem., 4 (9), 640–662.
DOI: https://doi.org/10.22146/ijc.40448
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