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Vol. 36 No. 3 (2024): Vol 36 Issue 3, 2024

Copyright (c) 2024 Bondada N.B. Vaidehi, Hymavathi Veeravarapu, Murali Krishna Kumar Muthyala

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

Docking Studies, Synthesis, SAR and Anti-TB Activity of Glycinamido Analogues

https://doi.org/10.14233/ajchem.2024.30798
Bondada N.B. Vaidehi
Department of Pharmaceutical Chemistry, Aditya College of Pharmacy, Surampalem-533437, India
https://orcid.org/0009-0003-2816-4031
Hymavathi Veeravarapu
Pharmaceutical Chemistry Research Lab, AU College of Pharmaceutical Sciences, Andhra University, Visakhapatnam-530003, India
https://orcid.org/0000-0001-7293-816X
Murali Krishna Kumar Muthyala
Pharmaceutical Chemistry Research Lab, AU College of Pharmaceutical Sciences, Andhra University, Visakhapatnam-530003, India
https://orcid.org/0000-0002-4766-7836

Corresponding Author(s) : Murali Krishna Kumar Muthyala

profmmkau@gmail.com

Asian Journal of Chemistry, Vol. 36 No. 3 (2024): Vol 36 Issue 3, 2024

Abstract

Mycolic acid is a crucial component of the Mycobacterium tuberculosis cell wall and mycolic acid methyltransferases (MAMTs) are essential for mycolic acids to mature. In the present study, an inhouse library of 330 ligands was designed taking glycinamido moiety as scaffold. Virtual screening was carried out with this library of compounds against MmaA1 as the target protein. About 55 hits were identified through docking, ADMET studies and these molecules were synthesized by the Schotten-Baumann reaction followed by a nucleophilic substitution reaction. All the compounds were subjected to in vitro anti-Tb screening by microplate alamar blue assay (MABA). The Mdb1, Mdb4 & Meb1 exhibited excellent activity against M. tuberculosis H37Rv bacilli strain with an MIC of 1.56 µg/mL. The SAR studies shows that the aryl ring attached directly to the nitrogen atom as present in 2(-N-substituted glycinamido) derivatives is essential for the compound to exhibit potent anti-TB activity.

Keywords

Glycinamido derivatives Mycolic acids Docking studies Mycobacterium tuberculosis
Vaidehi, B. N., Veeravarapu, H., & Muthyala, M. K. K. (2024). Docking Studies, Synthesis, SAR and Anti-TB Activity of Glycinamido Analogues. Asian Journal of Chemistry, 36(3), 549–570. https://doi.org/10.14233/ajchem.2024.30798
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References
  1. https://www.nhs.uk/conditions/tuberculosis-tb/#:~:text=Tuberculosis% 20(TB)%20is%20caused%20by,a%20long%20period%20of%20time
  2. T.B. Facts, https://www.cdc.gov/tb/worldtbday/history.html
  3. World Health Organization (WHO), Global Tuberculosis Report (2022); https://www.who.int/publications/i/item/9789240061729
  4. P. Miotto, Y. Zhang, D.M. Cirillo and W.C. Yam, Respirology, 23, 1098 (2018); https://doi.org/10.1111/resp.13393
  5. TB India Report (2022); http://www.tbcindia.gov.in (2022). Accessed on 25.03.2022.
  6. S. Tiberi, M. Muñoz-Torrico, R. Duarte, M. Dalcolmo, L. D’Ambrosio and G.-B. Migliori, Pulmonology, 24, 86 (2018); https://doi.org/10.1016/j.rppnen.2017.10.009
  7. C. Perrin, K. Athersuch, G. Elder, M. Martin and A. Alsalhani, BMJ Glob. Health, 7, e007490 (2022); https://doi.org/10.1136/bmjgh-2021-007490
  8. P.J. Brennan, Tuberculosis, 83, 91 (2003); https://doi.org/10.1016/s1472-9792(02)00089-6
  9. O. Zimhony, J.S. Cox, J.T. Welch, C. Vilchèze and W.R. Jacobs Jr, Nat. Med., 6, 1043 (2000); https://doi.org/10.1038/79558
  10. M.S. Glickman, J.S. Cox and W.R. Jacobs Jr., Mol. Cell, 5, 717 (2000); https://doi.org/10.1016/S1097-2765(00)80250-6
  11. M.A. Forrellad, L.I. Klepp, A. Gioffré, J. Sabio y García, H.R. Morbidoni, M.P. Santangelo, A.A. Cataldi and F. Bigi, Virulence, 4, 3 (2013); https://doi.org/10.4161/viru.22329
  12. K. Takayama, C. Wang and G.S. Besra, Clin. Microbiol. Rev., 18, 81 (2005); https://doi.org/10.1128/CMR.18.1.81-101.2005
  13. H. Veeravarapu, V. Malkhed, K.K. Mustyala, R. Vadija, R. Malikanti, U. Vuruputuri and M.K.K. Muthyala, Mol. Divers., 25, 351 (2021); https://doi.org/10.1007/s11030-020-10107-0
  14. H. Veeravarapu, M. Tirumalasetty, S.P. Kurati, U. Wunnava and M.K.K. Muthyala, Bioorg. Med. Chem. Lett., 30, 127603 (2020); https://doi.org/10.1016/j.bmcl.2020.127603
  15. G.M. Morris, R. Huey, W. Lindstrom, M.F. Sanner, R.K. Belew, D.S. Goodsell and A.J. Olson, J. Comput. Chem., 30, 2785 (2009); https://doi.org/10.1002/jcc.21256
  16. L. Schrodinger, The PyMOL Molecular Graphics System, Version 1.3r1 (2010).
  17. BIOVIA, Dassault Systemes, Discovery Studio Visualizer, v21.1.0.20298; Dassault Systemes: Sandiego, CA, USA (2021).
  18. A. Daina, O. Michielin and V. Zoete, Sci. Rep., 7, 42717 (2017); https://doi.org/10.1038/srep42717
  19. D.E.V. Pires, T.L. Blundell and D.B. Ascher, J. Med. Chem., 58, 4066 (2015); https://doi.org/10.1021/acs.jmedchem.5b00104
  20. Molinspiration Cheminformatics Free Web Services, Available online: https://www.molinspiration.com (accessed on 12 March 2023).
  21. J.L. Dahlin, J. Inglese and M.A. Walters, Nat. Rev. Drug Discov., 14, 279 (2015); https://doi.org/10.1038/nrd4578
  22. L. Di, Expert Opin. Drug Metab. Toxicol., 10, 379 (2014); https://doi.org/10.1517/17425255.2014.876006
  23. C.A. Lipinski, F. Lombardo, B.W. Dominy and P.J. Feeney, Adv. Drug Deliv. Rev., 23, 3 (1997); https://doi.org/10.1016/S0169-409X(96)00423-1
  24. A. Jarrahpour, J. Fathi, M. Mimouni, T.B. Hadda, J. Sheikh, Z. Chohan and A. Parvez, Med. Chem. Res., 21, 1984 (2012); https://doi.org/10.1007/s00044-011-9723-0
  25. S. Tahlan, K. Ramasamy, S. Lim, S.A. Shah, V. Mani and B. Narasimhan, Chem. Cent. J., 12, 139 (2018); https://doi.org/10.1186/s13065-018-0513-3
  26. S.G. Franzblau, R.S. Witzig, J.C. Mclaughlin, P. Torres, G. Madico, A. Hernandez, M.T. Degnan, M.B. Cook, V.K. Quenzer, R.M. Ferguson and R.H. Gilman, J. Clin. Microbiol., 36, 362 (1998); https://doi.org/10.1128/JCM.36.2.362-366.1998
  27. C.B. Inderlied and M. Salfinger, Antimicrobial Agents and Susceptibility Tests: Mycobacteria, Manual of Clinical Microbiology, ASM Press, Washington, edn. 6, p. 1385 (1995).
  28. M.A. Morgan, C.D. Horstmeier, D.R. DeYoung and G.D. Roberts, J. Clin. Microbiol., 18, 384 (1983); https://doi.org/10.1128/jcm.18.2.384-388.1983
  29. S. Ali, A. Ehtram, N. Arora, P. Manjunath, D. Roy, N.Z. Ehtesham and S.E. Hasnain, Front. Cell. Infect. Microbiol., 11, 622487 (2021); https://doi.org/10.3389/fcimb.2021.622487
  30. J. Dundas, Z. Ouyang, J. Tseng, A. Binkowski, Y. Turpaz and J. Liang, Nucleic Acids Res., 34, 116 (2006); https://doi.org/10.1093/nar/gkl282
  31. T. Halgren, Chem. Biol. Drug Des., 69, 146 (2007); https://doi.org/10.1111/j.1747-0285.2007.00483.x
  32. D. Schneidman-Duhovny, Y. Inbar, R. Nussinov and H.J. Wolfson, Nucleic Acids Res., 33, 363 (2005); https://doi.org/10.1093/nar/gki481
  33. J. Vaubourgeix, J.F. Bardou, F. Boisssier, S. Julien, P. Constant, O. Ploux, M. Daffe, A. Quemard, L. Mourey, J. Biol. Chem., 284, 19321 (2009); https://doi.org/10.1074/jbc.M809599200
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