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Abstract

Benzimidazole containing mercapto group at the 2nd position is attractive nucleus for the modification with wider pharmacological activities. The aim of this study is to design benzofused nitrogen containing heterocyclic derivatives of mercapto benzimidazole using molecular docking. Using an effective procedure, N-substituted mercapto benzimidazole derivatives was synthesized. The antimicrobial activity of all the synthesized compounds was tested against four different organisms viz. E. coli, Pseudomonas aeruginosa, Staphylococcus aureus and Candida albicans. Molecular docking of mercapto benzimidazole derivatives against DNA gyrase subunit B PDB: 5l3j and Staphylococcus aureus tyrosyl-tRNA synthetase PDB:1jij was performed using docking protocol. The compound binds to the active site of DNA gyrase subunit B (1KZN) in a docking study, indicating that it may have antimicrobial activity. Compounds MB3 and MB5 have good antimicrobial capacity whereas compound MB4 has the high activity against Candida albicans.

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Mercaptobenzimidazole Antimicrobial Molecular docking DNA gyrase Tyrosyl-tRNA synthetase in silico Screening.

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D. Patil, T., V. Amrutkar, S., & S. Jagdale, A. (2021). Design, in silico Analysis, Synthesis and Evaluation of Novel Benzofused Nitrogen Containing Heterocyclic N-Substituted Mercaptobenzimidazole Derivatives as Potential Antimicrobial Agent. Asian Journal of Organic & Medicinal Chemistry, 6(2), 121–127. https://doi.org/10.14233/ajomc.2021.AJOMC-P325
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References

  1. N.D. Mahesh Kumar and P.K. Dubey, An Expeditious Microwave-Assisted Synthesis of Mercapto Benzazoles, Quinazolinone and Oxadiazoles, J. Indian Chem., 51B, 1619 (2012).
  2. N. Bennamane, K. Zaïoua, Y. Akacem, R. Kaoua, Y. Bentarzi, S. Bakhta, B. Nedjar-Kolli and L. Ouhab, Synthesis of Benzimidazol-2-thiones from Dimedone : An Unexpected Cyclisation into a Five-Membered Ring, Org. Commun., 2, 49 (2009).
  3. M.R. Ahamed, S.F. Narren and A.S. Sadiq, Synthesis of 2-Mercapto-benzimidazole and Some of its Derivatives, J. Al-Nahrain Univ. Sci., 16, 77 (2013); https://doi.org/10.22401/jnus.16.2.11
  4. H.H. Amer, O.M. Ali and I.K. El-Kafaween, Synthesis of Some New Nucleosides Derived from 2-Mercapto Benzimidazole with Expected Biological Activity, Orient. J. Chem., 33, 2303 (2017); https://doi.org/10.13005/ojc/330519
  5. M.V. De Almeida, S.H. Cardoso, J.V. De Assis and M.V.N. De Souza, Synthesis of 2-Mercaptobenzothiazole and 2-Mercaptobenzimidazole Derivatives Condensed with Carbohydrates as a Potential Antimicrobial Agents, J. Sulfur Chem., 28, 17 (2007); https://doi.org/10.1080/17415990601055291
  6. R. Al-Kazweeny, Z.A. Muhi-eldeen, E. Al-kaissi and S. Al-Tameemi, Design, Synthesis, Structural Elucidation and Antimicrobial Evaluation of Various Derivatives of 2-Mercaptobenzimidazole as Possible Antimicrobial Agents, Int. J. Med. Res. Health Sci., 9, 1 (2020).
  7. E.G. Paronikyan, A.K. Oganisyan, A.S. Noravyan, R.G. Paronikyan and I.A. Dzhagatspanyan, Synthesis and Anticonvulsant Activity of Pyrano-[4¢,3¢:4,5]pyrido[2,3-b]furo[3,2-d]pyrimidine and Pyrano-[4¢,3¢:4,5]-pyrido[2,3-b]furo[3,2-d]pyridine Derivatives, Pharm. Chem. J., 36, 413 (2002); https://doi.org/10.1023/A:1021250208442
  8. S. Gupta, S.P. Gupta, N. Upmanyu and G. Garg, Synthesis and Biological Evaluation of 2-Mercaptobenzimidazole Derivatives as Anti-Inflammatory Agents, J. Drug Des. Med. Chem., 1, 12 (2015);
  9. K. Sakemi, R. Ito, T. Umemura, Y. Ohno and M. Tsuda, Comparative Toxicokinetic/Toxicodynamic Study of Rubber Antioxidants, 2-Mercapto-benzimidazole and its Methyl Substituted Derivatives by Repeated Oral Administration in Rats, Arch. Toxicol., 76, 682 (2002); https://doi.org/10.1007/s00204-002-0392-0
  10. A. Miyajima, K. Sakemi-Hoshikawa, M. Usami, K. Mitsunaga, T. Irie, Y. Ohno and M. Sunouchi, Thyrotoxic Rubber Antioxidants, 2-Mercaptobenzimidazole and its Methyl Derivatives, cause both Inhibition and Induction of Drug-metabolizing Activity in Rat Liver Microsomes after Repeated Oral Administration, Biochem. Biophys. Res. Commun., 492, 116 (2017); https://doi.org/10.1016/j.bbrc.2017.08.024
  11. T.L. Rebstock, C.D. Ball and C.L. Hamner, Inhibition of Plant Growth by 2-Mercaptobenzimidazole Analogs, Plant Physiol., 30, 382 (1955); https://doi.org/10.1104/pp.30.4.382
  12. S.A.M. Refaey, F. Taha and A.M. Abd El-Malak,Corrosion and Inhibition of 316L Stainless Steel in Neutral Medium by 2-Mercapto-benzimidazole, Int. J. Electrochem. Sci., 1, 80 (2006); https://doi.org/10.20964/1020080
  13. M.L. Wang and B.L. Liu, Synthesis of 2-Mercaptobenzimidazole from the Reaction of o-Phenylene Diamine and Carbon Disulfide in the Presence of Potassium Hydroxide, J. Chinese Inst. Chem. Eng., 38, 161 (2007); https://doi.org/10.1016/j.jcice.2007.01.003
  14. J.A.V. and B.D. Deacon, 2-Mercaptobenzimidazole (2-Benzimidazole-thiol), Org. Synth., 30, 56 (1950); https://doi.org/10.15227/orgsyn.030.0056
  15. R.V. Heralagi, K.N. Jayaveera and B. Shivkumar, Synthesis of Some Novel Bis Type 2-Mercapto Benzimidazole Derivatives, Res. J. Pharm. Biol. Chem. Sci., 3, 407 (2012).
  16. A.J. Harte and T. Gunnlaugsson, Synthesis of a-Chloroamides in Water, Tetrahedron Lett., 47, 6321 (2006); https://doi.org/10.1016/j.tetlet.2006.06.090
  17. D. Mishra, R. Singh and C. Rout, A Facile Amidation of Chloroacetyl Chloride using DBU, Int. J. ChemTech Res., 10, 365 (2017).
  18. P. Saxena, D.C.P. Singh, A. Ali and V. Sharma, Synthesis of Some Derivatives of 2-Mercaptobenzothiazole and their Evaluation as Anti-inflammatory Agents, Int. J. Pharm. Pharm. Sci., 5, 454 (2013).
  19. U.D. Bhagat S.S. Kotgire, S.K. Mahajan and S.V. Amrutkar, Synthesis of Ethyl 2-(2-methyl-4-oxoquinazolin-3(4H)-yl)acetate as Important Analog and Intermediate of 2,3-Disubstituted Quinazolinones, J. Pharm. Sci. Res., 2, 518 (2010).
  20. W.S. El-serwy, H.S. Mohamed, W.S. El-serwy, N.A. Mohamed, E.M.M. Kassem, E.S. Nossier and A.S.G. Shalaby, Molecular Docking Study of Newly Synthesized Thiopyrimidines as Antimicrobial Agents Targeting DNA Gyrase Enzyme, J. Heterocycl. Chem., 56, 2027 (2019); https://doi.org/10.1002/jhet.3583
  21. M. Aruna Kumari, S. Triloknadh, N. Harikrishna, M. Vijjulatha and C. Venkata Rao, Synthesis, Antibacterial Activity and Docking Studies of 1,2,3-triazole-Tagged Thieno[2,3-d]pyrimidinone Derivatives, J. Heterocycl. Chem., 54, 3672 (2017); https://doi.org/10.1002/jhet.2995
  22. T. Önkol, D.S. Dogruer, L. Uzun, S. Adak, S. Özkan and M.F. Sahin, Synthesis and Antimicrobial Activity of New 1,2,4-triazole and 1,3,4-thiadiazole Derivatives, J. Enzyme Inhib. Med. Chem., 23, 277 (2008); https://doi.org/10.1080/14756360701408697
  23. W.W.N. Al-Kaissy, H.F. Safaa, S. Tuama and M.H. Al-Majidi, Synthesis, Characterization and Evaluation of Antimicrobial Activity of Some New Acetylenic Amine and 2-oxoazetidine of Carbazole, Am. J. Sci. Ind. Res, 4, 389 (2013).
  24. N.M. O’Boyle, M. Banck, C.A. James, C. Morley, T. Vandermeersch and G.R. Hutchison, Open Babel: An Open Chemical Toolbox, J. Cheminform., 3, 33 (2011); https://doi.org/10.1186/1758-2946-3-33
  25. W.L. DeLano, Newsl. Protein Crystallogr., 40, 82 (2002).
  26. A. Allouche, Gabedit—A Graphical User Interface for Computational Chemistry Softwares, J. Comput. Chem., 32, 174 (2011); https://doi.org/10.1002/jcc.21600
  27. BIOVIA, Dassault Systèmes, San Diego: Dassault Systèmes (2017).
  28. M. Gjorgjieva, T. Tomašiè, M. Baranèokova, S. Katsamakas, J. Ilaš, P. Tammela, L. Peterlin Mašiè and D. Kikelj, Discovery of Benzothiazole Scaffold-Based DNA Gyrase B Inhibitors, J. Med. Chem., 59, 8941 (2016); https://doi.org/10.1021/acs.jmedchem.6b00864
  29. O.A. Durojaye, N. Ugochi, C. Samuel and E.N. Akpan, in silico Structure-Activity Relationship and Molecular Docking Study of Levofloxacin and its Monosubstitted Analogues against the Escherichia coli DNA Gyrase, Int. J. Chem. Pharm. Sci., 6, 1 (2018); https://doi.org/10.13140/RG.2.2.26190.72009
  30. M.A. Islam and T.S. Pillay, Identification of Promising Anti-DNA Gyrase Antibacterial Compounds using de novo Design, Molecular Docking and Molecular Dynamics Studies, J. Biomol. Struct. Dyn., 38, 1798 (2020); https://doi.org/10.1080/07391102.2019.1617785
  31. M.B. Pisano, A. Kumar, R. Medda, G. Gatto, R. Pal, A. Fais, B. Era, S. Cosentino, E. Uriarte, L. Santana, F. Pintus and M.J. Matos, Antibacterial Activity and Molecular Docking Studies of a Selected Series of Hydroxy-3-arylcoumarins, Molecules, 24, 2815 (2019); https://doi.org/10.3390/molecules24152815
  32. K. Gullapelli, G. Brahmeshwari, M. Ravichander and U. Kusuma, Synthesis, Antibacterial and Molecular Docking Studies of New Benzimidazole Derivatives, Egypt. J. Basic Appl. Sci., 4, 303 (2017); https://doi.org/10.1016/j.ejbas.2017.09.002
  33. F. Athar, S. Ansari and M.A. Beg, Molecular Docking Studies of Calotropis gigantea Phytoconstituents against Staphylococcus aureus tyrosyl-tRNA Synthetase Protein, J. Bacteriol. Mycol., 8, 78 (2020); https://doi.org/10.15406/jbmoa.2020.08.00278
  34. A. Daina, O. Michielin and V. Zoete, SwissADME: A Free Web Tool to Evaluate Pharmacokinetics, Drug-likeness and Medicinal Chemistry Friendliness of Small Molecules, Sci. Rep., 7, 42717 (2017); https://doi.org/10.1038/srep42717
  35. M.A. de Brito, Pharmacokinetic Study with Computational Tools in the Medicinal Chemistry Course, Braz. J. Pharm. Sci., 47, 797 (2011); https://doi.org/10.1590/S1984-82502011000400017
  36. C.A. Lipinski, Lead- and Drug-like Compounds: The Rule-of-Five Revolution, Drug Discov. Today. Technol., 1, 337 (2004); https://doi.org/10.1016/j.ddtec.2004.11.007
  37. G. Sliwoski, S. Kothiwale, J. Meiler and E.W. Lowe Jr., Computational Methods in Drug Discovery, Pharmacol. Rev., 66, 334 (2014); https://doi.org/10.1124/pr.112.007336
  38. A.K. Ghose, V.N. Viswanadhan and J.J. Wendoloski, A Knowledge-Based Approach in Designing Combinatorial or Medicinal Chemistry Libraries for Drug Discovery. 1. A Qualitative and Quantitative Characterization of Known Drug Databases, J. Comb. Chem., 1, 55 (1999); https://doi.org/10.1021/cc9800071