Design, Synthesis and Antimicrobial Evaluation of Novel 2-Thiobenzimidazole Derivatives: in silico and in vitro Approach

C. Naresh Babu; S. Triveni; M. Vijaya Jyothi; B. Yamuna; A. Yamini

doi:10.14233/ajchem.2020.22821

Issue

Vol. 32 No. 11 (2020): Vol 32 Issue 11

Issue Published : October 28, 2020

This work is licensed under a Creative Commons Attribution 4.0 International License.

Design, Synthesis and Antimicrobial Evaluation of Novel 2-Thiobenzimidazole Derivatives: in silico and in vitro Approach

https://doi.org/10.14233/ajchem.2020.22821

C. Naresh Babu

Molecular Modeling and Drug Discovery Division, RERDS-CPR, Raghavendra Institute of Pharmaceutical Education and Research (RIPER)-Autonomous, K.R. Palli Cross, Near SK University, Anantapur-515721, India

S. Triveni

Department of Pharmaceutical Chemistry, Raghavendra Institute of Pharmaceutical Education and Research (RIPER)-Autonomous, K.R. Palli Cross, Near SK University, Anantapur-515721, India

M. Vijaya Jyothi

Department of Pharmaceutical Chemistry, Raghavendra Institute of Pharmaceutical Education and Research (RIPER)-Autonomous, K.R. Palli Cross, Near SK University, Anantapur-515721, India

B. Yamuna

Department of Pharmaceutical Chemistry, Raghavendra Institute of Pharmaceutical Education and Research (RIPER)-Autonomous, K.R. Palli Cross, Near SK University, Anantapur-515721, India

A. Yamini

Department of Pharmaceutical Chemistry, Raghavendra Institute of Pharmaceutical Education and Research (RIPER)-Autonomous, K.R. Palli Cross, Near SK University, Anantapur-515721, India

Corresponding Author(s) : S. Triveni

s.trivenipharma@gmail.com

Asian Journal of Chemistry, Vol. 32 No. 11 (2020): Vol 32 Issue 11
Article Published : October 28, 2020

Abstract

The development of potent antimicrobial agents is more essential due to resistance developed in microorganisms towards the existing drugs. The diversity in the biological retort profile of benzimidazole more attracted the attention to develop novel compounds to its various potential against microorganisms. In present work, designed molecular structures docked against DNA gyrase subunit B and lanosterol 14α-demethylase (LAD) proteins. Interestingly, most of the compounds revealed excellent docking scores and interactions compared with the co-crystal ligands KKK, 1YN of LAD proteins 3LD6, 5V5Z than DNA gyrase subunit B proteins 5L3J and 4P8O. Then, the molecular properties were predicted by the Swiss ADME tool, the compounds showed no violation in Lipinski’s rule and good synthetic accessibility. These compounds synthesized by stirring of 2-mercapto benzimidazole (1), epichlorohydrin (2) in the presence of sodium hydroxide gives 1-(1H-benzo[d]imidazole-2-ylthio)-3-chloropropan-2-ol (3), which upon refluxing with different substituted aliphatic and aromatic amines in methanol produces novel benzimidazole derivatives (4a-l). These compounds were characterized by their melting point, FT-IR, ¹H NMR and Mass spectral data. The synthesized molecules screened for antibacterial and antifungal activity. The compound 4l exhibited excellent activity at MIC 0.4 μg/mL against C. albicans. Compounds 4c and 4e showed MIC at 3.12 μg/mL against E. coli and the compounds 4l and 4j exhibited MIC at 3.12 μg/mL against S. aureus. Docking studies and activity result reveals the novel benzimidazole compound 4l has excellent antifungal and antibacterial effect.

Keywords

Benzimidazole Swiss ADME Molecular docking studies Antibacterial activity Antifungal activity

Naresh Babu, C., Triveni, S., Vijaya Jyothi, M., Yamuna, B., & Yamini, A. (2020). Design, Synthesis and Antimicrobial Evaluation of Novel 2-Thiobenzimidazole Derivatives: in silico and in vitro Approach. Asian Journal of Chemistry, 32(11), 2753–2762. https://doi.org/10.14233/ajchem.2020.22821

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References

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References

N. Jackson, L. Czaplewski and L.J.V. Piddock, J. Antimicrob. Chemother., 73, 1452 (2018); https://doi.org/10.1093/jac/dky019

Salahuddin, M. Shaharyar and A. Mazumder, Arab. J. Chem., 10(Supl. 1), S157 (2017); https://doi.org/10.1016/j.arabjc.2012.07.017

A.T. Mavrova, K.K. Anichina, D.I. Vuchev, J.A. Tsenov, P.S. Denkova, M.S. Kondeva and M.K. Micheva, Eur. J. Med. Chem., 41, 1412 (2006); https://doi.org/10.1016/j.ejmech.2006.07.005

F. Hobrecker, Ber., 5, 920 (1872); https://doi.org/10.1002/cber.18720050295

M. Tuncbilek, T. Kiper and N. Altanlar, Eur. J. Med. Chem., 44, 1024 (2009); https://doi.org/10.1016/j.ejmech.2008.06.026

A.K. Tewari and A. Mishra, Indian J. Chem., 45B, 489 (2006).

R.D. Haugwitz, R.G. Angel, G.A. Jacobs, B.V. Maurer, V.L. Narayanan, L.R. Cruthers and J. Szanto, J. Med. Chem., 25, 969 (1982); https://doi.org/10.1021/jm00350a017

M. Gjorgjieva, T. Tomasic, M. Barancokova, S. Katsamakas, J. Ilas, P.Tammela, L.P. Masic and D. Kikelj, J. Med. Chem., 59, 8941 (2016); https://doi.org/10.1021/acs.jmedchem.6b00864

A.-L. Grillot, A.L. Tiran, D. Shannon, E. Krueger, Y. Liao, H. O’Dowd, Q. Tang, S. Ronkin, T. Wang, N. Waal, P. Li, D. Lauffer, E. Sizensky, J. Tanoury, E. Perola, T.H. Grossman, T. Doyle, B. Hanzelka, S. Jones, V.Dixit, N. Ewing, S. Liao, B. Boucher, M. Jacobs, Y. Bennani and P.S. Charifson, J. Med. Chem., 57, 8792 (2014); https://doi.org/10.1021/jm500563g

N. Strushkevich, S.A. Usanov and H.-W. Park, J. Mol. Biol., 397, 1067 (2010); https://doi.org/10.1016/j.jmb.2010.01.075

M.V. Keniya, M. Sabherwal, R.K. Wilson, M.A. Woods, A.A. Sagatova and D.A. Joel, Antimicrob. Agents Chemother., 62, e01134 (2018); https://doi.org/10.1128/AAC.01134-18

A. Daina, O. Michielin and V. Zoete, Sci. Rep., 7, 42717 (2017); https://doi.org/10.1038/srep42717

A. Daina, O. Michielin and V. Zoete, J. Chem. Inf. Model., 54, 3284 (2014); https://doi.org/10.1021/ci500467k

A. Daina and V. Zoete, ChemMedChem, 11, 1117 (2016); https://doi.org/10.1002/cmdc.201600182

R. Schwalve, L.S. Moore and A.V. Goodwin, Antimicrobial Susceptibility Testing Protocols, CRC Press (2007).

H.D. Isenberg and L.S. Garcia, Clinical Microbiology Procedures Handbook, American Society for Microbiology, ASM Press Washington, DC, Vol 1 (2007).

Issue

Vol. 32 No. 11 (2020): Vol 32 Issue 11

Design, Synthesis and Antimicrobial Evaluation of Novel 2-Thiobenzimidazole Derivatives: in silico and in vitro Approach

Corresponding Author(s) : S. Triveni

Abstract

Keywords

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