A holistic molecular modelling approach to design novel indole-2-carboxamide derivatives as potential inhibitors of MmpL3

References

• Tuberculosis [Internet], World Health Organization; [Cited 2022 Jan 21]; Available at https://www.who.int/health-topics/tuberculosis#tab=tab_1.
   Google Scholar
• Tuberculosis [Internet], World Health Organization; 2021 Oct 14 [Cited 2022 Mar 27]; Available at https://www.who.int/news-room/fact-sheets/detail/tuberculosis.
   Google Scholar
• Tuberculosis deaths rise for the first time in more than a decade due to the COVID-19 pandemic [Internet], World Health Organization; 2021 Oct 4 [Cited 2022 Apr 4]; Available at https://www.who.int/news/item/14-10-2021-tuberculosis-deaths-rise-for-the-first-time-in-more-than-a-decade-due-to-the-covid-19-pandemic.
   Google Scholar
• H.N. Jnawali and S. Ryoo, First– And second–line drugs and drug resistance, in Tuberculosis, B.H. Mahboub and M.G. Vats, eds., IntechOpen, 2013, Available at https://www.intechopen.com/chapters/43723.
   Google Scholar
• M. Shao, M. McNeil, G.M. Cook, and X. Lu, MmpL3 inhibitors as antituberculosis drugs, Eur. J. Med. Chem. 200 (2020), pp. 112390. doi:10.1016/j.ejmech.2020.112390.
   PubMed Web of Science ®Google Scholar
• T.R. Ioerger, T. O’Malley, K.M. Guinn, M.J. Hickey, K.C. Murphy, K.C. Murphy, H.I.M. Boshoff, E.J. Rubin, E.J. Rubin, C.M. Sassetti, D.R.S. C.E. Barry III, T. Parish, and J.C. Sacchettin, Identification of new drug targets and resistance mechanisms in Mycobacterium tuberculosis, PloS One 8 (2013), pp. e75245. doi:10.1371/journal.pone.0075245.
   PubMedGoogle Scholar
• A. Campaniço, R. Moreira, and F. Lopes, Drug discovery in tuberculosis. New drug targets and antimycobacterial agents, Eur. J. Med. Chem. 150 (2018), pp. 525–554. doi:10.1016/j.ejmech.2018.03.020.
   PubMed Web of Science ®Google Scholar
• M.D. Umare, P.B. Khedekar, and R.V. Chikhale, Mycobacterial membrane protein large 3 (MmpL3) Inhibitors: A promising approach to combat tuberculosis, ChemMedChem 16 (2021), pp. 3136–3148. doi:10.1002/cmdc.202100359.
   PubMed Web of Science ®Google Scholar
• J.R. Bolla, Targeting MmpL3 for anti-tuberculosis drug development, Biochem. Soc. Trans. 48 (2020), pp. 1463–1472. doi:10.1042/BST20190950.
   PubMed Web of Science ®Google Scholar
• A.E. Grzegorzewicz, H. Pham, V.A.K.B. Gundi, M.S. Scherman, E.J. North, T. Hess, V. Jones, V. Gruppo, S.E.M. Born, J. Korduláková, S.S. Chavadi, C. Morisseau, A.J. Lenaerts, R.E. Lee, M.R. McNeil, and M. Jackson, Inhibition of mycolic acid transport across the Mycobacterium tuberculosis plasma membrane, Nat. Chem. Biol. 8 (2012), pp. 334–341. doi:10.1038/nchembio.794.
   PubMed Web of Science ®Google Scholar
• C. Su, P.A. Klenotic, J.R. Bolla, G.E. Purdy, C.V. Robinson, and E.W. Yu, MmpL3 is a lipid transporter that binds trehalose monomycolate and phosphatidylethanolamine, PNAS 116 (2019), pp. 11241–11246. doi:10.1073/pnas.1901346116.
   PubMed Web of Science ®Google Scholar
• G. Degiacomi, A. Benjak, J. Madacki, F. Boldrin, R. Provvedi, G. Palù, J. Kordulakova, S.T. Cole, and R. Manganelli, Essentiality of mmpL3 and impact of its silencing on Mycobacterium tuberculosis gene expression, Sci. Rep. 7 (2017), pp. 43495. doi:10.1038/srep43495.
   PubMed Web of Science ®Google Scholar
• J. Stec, O.K. Onajole, S. Lun, H. Guo, B. Merenbloom, G. Vistoli, W.R. Bishai, and A.P. Kozikowski, Indole-2-carboxamide-based MmpL3 inhibitors show exceptional antitubercular activity in an animal model of tuberculosis infection, J. Med. Chem. 59 (2016), pp. 6232–6247. doi:10.1021/acs.jmedchem.6b00415.
   PubMed Web of Science ®Google Scholar
• G. Poce, S. Consalvi, and M. Biava, MmpL3 inhibitors: Diverse chemical scaffolds inhibit the same target, Mini Rev. Med. Chem. 16 (2016), pp. 1274–1283. doi:10.2174/1389557516666160118105319.
   PubMed Web of Science ®Google Scholar
• B. Zhang, J. Li, X. Yang, L. Wu, J. Zhang, Y. Yang, Y. Zhao, L. Zhang, X. Yang, X. Yang, X. Cheng, Z. Liu, B. Jiang, H. Jiang, L.W. Guddat, H. Yang, and Z. Rao, Crystal structures of membrane transporter MmpL3, an anti-TB drug target, Cell 176 (2019), pp. 636–648. doi:10.1016/j.cell.2019.01.003.
   PubMed Web of Science ®Google Scholar
• O. Adams, J.C. Deme, J.L. Parker, C. Consortium, P.W. Fowler, S.M. Lea, and S. Newstead, Cryo-EM structure and resistance landscape of M. tuberculosis MmpL3: An emergent therapeutic target, Structure 29 (2021), pp. 1182–1191. doi:10.1016/j.str.2021.06.013.
   PubMed Web of Science ®Google Scholar
• O.K. Onajole, M. Pieroni, S.K. Tipparaju, S. Lun, J. Stec, G. Chen, H. Gunosewoyo, H. Guo, N.C. Ammerman, W.R. Bishai, and A.P. Kozikowski, Preliminary structure–activity relationships and biological evaluation of novel antitubercular indolecarboxamide derivatives against drug-susceptible and drug-resistant Mycobacterium tuberculosis strains, J. Med. Chem. 56 (2013), pp. 4093–4103. doi:10.1021/jm4003878.
   PubMed Web of Science ®Google Scholar
• T.M. Dhameliyaa, K.I. Patel, R. Tiwari, S.K. Vagolu, D. Panda, D. Sriram, and A.K. Chakraborti, Design, synthesis, and biological evaluation of benzo[d]imidazole-2-carboxamides as new anti-TB agents, Bioorg. Chem. 107 (2021), pp. 104538. doi:10.1016/j.bioorg.2020.104538.
   PubMed Web of Science ®Google Scholar
• K.A. Bhakhar, N.D. Gajjar, K.B. Bodiwala, D.K. Sureja, and T.M. Dhameliya, Identification of anti-mycobacterial agents against mmpL3: Virtual screening, ADMET analysis and MD simulations, J. Mol. Struct. 1244 (2021), pp. 130941. doi:10.1016/j.molstruc.2021.130941.
   Web of Science ®Google Scholar
• J. Jiricek, R.R. Kondreddy, and P.W. Smith, Indole Carboxamide Derivatives And Uses Thereof, World Intellectual Property Organization, International Publication Number WOR 2014/037900 Al., International Publication Number WOR 2014/037900 Al.
   Google Scholar
• P. Manogara, S. Vijayakumara, S. Rajalakshmia, M. Pugazhenthib, P.K. Praseethac, and S. Jayanthid, In silico studies on CNR1 receptor and effective cyanobacterial drugs: Homology modelling, molecular docking and molecular dynamic simulations, Gene Rep. 17 (2019), pp. 100505. doi:10.1016/j.genrep.2019.100505.
   Web of Science ®Google Scholar
• R. Ray, S.R. Birangal, F. Fathima, H.I. Boshoff, H.E. Forbes, R.C. Hariharapura, and G.G. Shenoy, Molecular insights into Mmpl3 lead to the development of novel indole-2-carboxamides as antitubercular agents, Mol. Syst. Des. Eng, Advance Article, 2022. Available at https://pubs.rsc.org/en/content/articlelanding/2022/me/d1me00122a.
   Google Scholar
• G.M. Sastry, M. Adzhigirey, T. Day, R. Annabhimoju, and W. Sherman, Protein and ligand preparation: Parameters, protocols, and influence on virtual screening enrichments, J. Comput. Aided Mol. Des 27 (2013), pp. 221–234. doi:10.1007/s10822-013-9644-8.
   PubMed Web of Science ®Google Scholar
• M.J. Lobo, R. Ray, and G.G. Shenoy, Gaining deeper insights into the surface binding of Bedaquiline analogues with the ATP synthase subunit C of Mycobacterium tuberculosis using molecular docking, molecular dynamics simulation and 3D-QSAR techniques, New J. Chem 44 (2020), pp. 18831–18852. doi:10.1039/D0NJ02062A.
   Web of Science ®Google Scholar
• P.K. Murthya, V. Suneetha, S. Armaković, S.J. Armaković, P.A. Suchetane, L. Girif, and R.S. Rao, Synthesis, characterization and computational study of the newly synthetized sulfonamide molecule, J. Mol. Struct. 1153 (2017), pp. 212–229. doi:10.1016/j.molstruc.2017.10.028.
   Web of Science ®Google Scholar
• L. Ivanova, J. Tammiku-Taul, A.T. García-Sosa, Y. Sidorova, M. Saarma, and M. Karelson, Molecular dynamics simulations of the interactions between glial cell line-derived neurotrophic factor family receptor GFRα1 and small-molecule ligands, ACS Omega 3 (2018), pp. 11407–11414. doi:10.1021/acsomega.8b01524.
   PubMed Web of Science ®Google Scholar
• P. Kirubakaran, K. Muthusamy, K.H.D. Singh, and S. Nagamani, Ligand-based pharmacophore modeling; Atom-based 3D-QSAR analysis and molecular docking studies of phosphoinositide-dependent kinase-1 inhibitors, Indian J. Pharm. Sci. 74 (2012), pp. 141–151. doi:10.4103/0250-474X.103846.
   PubMed Web of Science ®Google Scholar
• R.A. Friesner, R.B. Murphy, M.P. Repasky, L.L. Frye, J.R. Greenwood, T.A. Halgren, P.C. Sanschagrin, and D.T. Mainz, Extra precision glide:  Docking and scoring incorporating a model of hydrophobic enclosure for protein−ligand complexes, J. Med. Chem. 49 (2006), pp. 6177–6196. doi:10.1021/jm051256o.
   PubMed Web of Science ®Google Scholar
• R.A. Friesner, J.L. Banks, R.B. Murphy, T.A. Halgren, J.J. Klicic, D.T. Mainz, M.P. Repasky, E.H. Knoll, M. Shelley, J.K. Perry, D.E. Shaw, P. Francis, and P.S. Shenkin, Glide:  A new approach for rapid, accurate docking and scoring. 1. Method and assessment of docking accuracy, J. Med. Chem. 47 (2004), pp. 1739–1749. doi:10.1021/jm0306430.
   PubMed Web of Science ®Google Scholar
• A. Mohan, R. Kirubakaran, J.A. Parray, R. Sivakumar, E. Murugesh, and M. Govarthanan, Ligand-based pharmacophore filtering, atom based 3D-QSAR, virtual screening and ADME studies for the discovery of potential ck2 inhibitors, J. Mol. Struct. 1205 (2020), pp. 127670. doi:10.1016/j.molstruc.2019.127670.
   Web of Science ®Google Scholar
• S.S.R. Alsayed, S. Lun, A.W. Bailey, A. Suri, C. Huang, M. Mocerino, A. Payne, S.T. Sredni, W.R. Bishai, and H. Gunosewoyo, Design, synthesis and evaluation of novel indole-2-carboxamides for growth inhibition of Mycobacterium tuberculosis and paediatric brain tumour cells, RSC Adv. 11 (2021), pp. 15497–15511. doi:10.1039/D0RA10728J.
   PubMed Web of Science ®Google Scholar
• S.S.R. Alsayed, S. Lun, G. Luna, C.C. Beh, A.D. Payne, N. Foster, W.R. Bishai, and H. Gunosewoyo, Design, synthesis, and biological evaluation of novel arylcarboxamide derivatives as anti-tubercular agents, RSC Adv. 10 (2020), pp. 7523–7540. doi:10.1039/C9RA10663D.
   PubMed Web of Science ®Google Scholar