K Poojita, Fajeelath Fathima, Rajdeep Ray, Lalit Kumar, Ruchi Verma
firstname.lastname@example.org , email@example.com
K Poojita1, Fajeelath Fathima1, Rajdeep Ray1, Lalit Kumar2, Ruchi Verma1*
1Department of Pharmaceutical Chemistry, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Madhav Nagar - 576104, Manipal, Udupi, Karnataka, India.
2Department of Pharmaceutics, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Madhav Nagar - 576104, Manipal, Udupi, Karnataka, India.
Volume - 14,
Issue - 12,
Year - 2021
Tuberculosis is one of the leading cause of increase in mortality rate in today’s health care scenario. Due to increase frequency of drug resistant TB it is prudent to find new targets and promising targets for anti-tubercular activity. MmpL3 (Mycobacterial Membrane Protein Large 3) is one of the most effective and promiscuous targets for development of new drug for anti-tubercular therapy due to its cross resistance inhibition property. In this study we have presented atom based 3D QSAR and finger print based 2D QSAR models to study different structural and functional groups of Adamantyl urea derivatives and their action in MmpL3 inhibitory activity which will provide us the insight for designing better and far more effective anti TB drugs.
Cite this article:
K Poojita, Fajeelath Fathima, Rajdeep Ray, Lalit Kumar, Ruchi Verma. Atom based 3D QSAR and Fingerprint based 2D QSAR of Novel Molecules as MmpL3 receptor inhibitors for Mycobacterium tuberculosis. Research Journal of Pharmacy and Technology. 2021; 14(12):6321-9. doi: 10.52711/0974-360X.2021.01093
K Poojita, Fajeelath Fathima, Rajdeep Ray, Lalit Kumar, Ruchi Verma. Atom based 3D QSAR and Fingerprint based 2D QSAR of Novel Molecules as MmpL3 receptor inhibitors for Mycobacterium tuberculosis. Research Journal of Pharmacy and Technology. 2021; 14(12):6321-9. doi: 10.52711/0974-360X.2021.01093 Available on: https://www.rjptonline.org/AbstractView.aspx?PID=2021-14-12-23
1. Singh S, Kumar S. Tuberculosis in India: Road to elimination. Int J Prev Med 2019; 10:114.
2. World Health Organisation. Global Tuberculosis Report 2019. Accessed on January 2020.
3. Chih-Chia Su, Philip A. Klenotic, Jani Reddy Bolla, Georgiana E. Purdy, Carol V. Robinson, Edward W. MmpL3 is a lipid transporter that binds Trehalose Monomycolates and phosphatidylethanolamine. Proceedings of the National Academy of Sciences 2019;116 (23) 11241-11246
4. Grzegorzewicz AE, Pham H, Gundi VA, et al. Inhibition of mycolic acid transport across the Mycobacterium tuberculosis plasma membrane. Nat Chem Biol. 2012; 8(4):334‐341.
5. Rayasam GV. MmpL3 a potential new target for development of novel anti-tuberculosis drugs. Expert Opin Ther Targets. 2014; 18(3):247‐256.
6. Kumar L, Verma R. Molecular docking based approach for the design of novel flavone analogues as inhibitor of beta-hydroxyacyl-ACP dehydratase HadAB complex. Research J. of Pharm. and tech. 10(8); 2439-2445.
7. Lohit T, Kumar L, Verma R. Design, Molecular Docking, ADME Analysis and Molecular Dynamics Studies of Novel Acetylated Schiff bases as COX-2 inhibitors. Research J. Pharm. and Tech. 13(4); 1901-1906.
8. Ruchi V, Indira B, Mradul T, Varadaraj BG· Gautham GS. In silico studies, synthesis and anticancer activity of novel diphenyl ether-based pyridine derivatives. Molecular diversity. 23; 2019: 541–554.
9. Ruchi V, Helena IMB, Kriti A, Indira B., Mradul T, Varadral GB, Gautham GS. Synthesis, antitubercular evaluation, molecular docking and molecular dynamics studies of 4,6-disubstituted-2-oxo-dihydropyridine-3-carbonitriles. Journal of molecular structure.1197:2019:117-133.
10. Ruchi V, Helena IMB, Kriti A, Indira B., Mradul T, Varadral GB, Gautham GS. Synthesis, evaluation, molecular docking, and molecular dynamics studies of novel N-(4-[pyridin-2-yloxy]benzyl) arylamine derivatives as potential antitubercular agents. Drug Dev Res. 2020;81:315–328.
11. Prem SM, Ravichandiran V, Aanandhi MV. Design, Synthesis and in silico molecular docking study of N-carbamoyl-6-oxo-1-phenyl-1, 6-dihydropyridine-3-carboxamide derivatives as fibroblast growth factor 1 inhibitor. Research Journal of Pharmacy and technology. 10(8); 2017:2527-2534.
12. Habeela JN, Raja MKMM. In silico molecular docking studies on the chemical constituents of clerodendrum phlomidis for its cytotoxic potential against breast cancer markers. Research Journal of Pharmacy and technology. 11 (4); 1612-1618:2018.
13. Surakanti R, Eppakayala L, Ramchander M, Venkat RP. Synthesis and molecular docking for anti-inflammatory and anti-mitotic activities of (S)-(2-Methyl-4-(1-Phenyl-1h-Thieno/Furan [3, 2-C] Pyrazol-3-yl) Piperazin-1-yl) (Pyridin-2-yl) Methanone. Asian Journal of Research in Chemistry. 10(4); 2017:582-586.
14. Hemalatha K, Chakkaravarthi V, Ganesa Murthy K, Kayatri R, Girija K. Molecular Properties and Docking Studies of Benzimidazole Derivatives as Potential Peptide Deformylase Inhibitors. Asian Journal of Research in Chemistry. 7(7); 2014: 644-648.
15. North, E.J., Scherman, M.S., Bruhn, D.F., Scarborough, J.S., Maddox, M.M., Jones, V., Grzegorzewicz, A., Yang, L., Hess, T., Morisseau, C., Jackson, M., McNeil, M.R., Lee, R.E. Design, synthesis and anti-tuberculosis activity of 1-adamantyl-3- heteroaryl ureas with improved in vitro pharmacokinetic properties. Bioorg Med Chem 2013; 21 (9), pp. 2587-2599
16. Wadhwa P, Bagchi S, Sharma A. 3D-QSAR Selectivity Analysis of 1-Adamantyl-3-Heteroaryl Urea Analogs as Potent Inhibitors of Mycobacterium tuberculosis. Curr Comput Aided Drug Des. 2015; 11(2):164‐183.
17. Ul-Haq Z, Effendi JS, Ashraf S, Bkhaitan MM. Atom and receptor based 3D QSAR models for generating new conformations from pyrazolopyrimidine as IL-2 inducible tyrosine kinase inhibitors. J Mol Graph Model. 2017; 74: 379‐395.
18. Wang M, Li W, Wang Y, Song Y, Wang J, Cheng M. In silico insight into voltage-gated sodium channel 1.7 inhibition for anti-pain drug discovery. J Mol Graph Model. 2018; 84:18‐28.
19. Kristam R, Parmar V, Viswanadhan VN. 3D-QSAR analysis of TRPV1 inhibitors reveals a pharmacophore applicable to diverse scaffolds and clinical candidates. J Mol Graph Model. 2013; 45: 157‐172.
20. An Y, Sherman W, Dixon SL. Kernel-based partial least squares: application to fingerprint-based QSAR with model visualization. J Chem Inf Model. 2013; 53(9):2312‐2321.
21. Kunal Roy, Rudra Narayan Das. A Review on Principles, Theory and Practices of 2D-QSAR. Curr. Drug Metab, 2014; 15, 346-379.
22. Ganatra S. H., Patle M. R, Bhagat G. K. Studies of Quantitative Structure-Activity Relationship (QSAR) of Hydantoin Based Active Anti-Cancer Drugs. Asian J. Research Chem. 2011; 4(10): 1643-1648.
23. R. S. Kalkotwar, R. B. Saudagar. Synthesis and QSAR Studies of Some 2,5-Diaryl Substituted-1,3,4-Oxadiazole Derivatives. Asian J. Research Chem. 2013, (11): 985-991.
24. Ashish Mullani, J. I. Disouza. Synthesis and QSAR study of N-Substituted [5-(1H-1,2,4-Triazol-5-yl)pyridine-2-YL]methanimine Derivatives as potential Antibacterial. Asian J. Research Chem. 2015, 8(9): 561-565.
25. V. S. Kawade, S. S. Kumbhar, P. B. Choudhari, M. S. Bhatia. 3D QSAR and Pharmacophore Modelling of some Pyrimidine Analogs as CDK4 Inhibitors. Asian J. Research Chem 2015; 8(4): 231-235.