In-silico predictive binding affinity and ADMET of novel n-[5-(2-fluorophenyl)-1, 3, 4-oxadiazole-carboxamide derivatives towards prot
Abstract
Abstract: The present study experimentally investigated the nitro-substituted heteroaromatic carboxamidesas effective against PKnGof Mycobacterium tuberculosis. Here we designed 15 heteroaromatic carboxamides[A1-B5]. The activities of the compounds can be explained in terms of docking results and biological activity by ADMET prediction. Protein Kinase G is a thioredoxin-fold containing eukaryoticlike serine/threonine Protein Kinase is a virulence factor in Mycobacterium tuberculosis. In present study the compounds A7, A2, A5& A6 are the candidates that shows the good results in Molecular Docking and these are tested against the reference compound that is stand Anti-TB agent Isoniazid.
Keywords:
Mycobacterium tuberculosis, PKnG, Carboxamide, Heteroaromatic, Molecular Docking, ADMET, Isoniazid
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References
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2. 3.Mostashari-Rad T, Arian R, Sadri H, Mehridehnavi A, Mokhtari M, Ghasemi F, Fassihi A. Study of CXCR4 chemokine receptor inhibitors using QSPR and mo-lecular docking methodologies. Journal of Theoretical and Computational Chemistry. 2019 Jun 3;18(04):1950018.
3. Jain, A.; Mondal, R. Extensively drug-resistant tuber-culosis:current challenges and threats. FEMS Immu-nol Med. Microbiol. 2008,53 (2), 145−150
4. Functional Groups in Organic Chemistry (thoughtco.com)
5. Vaghani H, Patel S and Patel S: 1, 3, 4-oxadiazole and its potency: a review. Int J Pharm Sci & Res 2021; 12(10): 5292-99. doi: 10.13040/ IJPSR.0975-8232.12(10).5292-99. 7.Chakraborti PK, Matange N, Nandicoori VK, Singh Y, Tyagi JS, Visweswariah SS. Signalling mechanisms in Mycobacteria. Tuberculosis. 2011 Sep 1;91(5):432-40.
6. Martínez R, Zamudio G, Pretelin-Castillo G, Torres-Ochoa R, Medina-Franco J, Espitia Pinzón C, Miranda M, Hernández E, Alanís-Garza B. Synthesis and antitubercular activity of-new N[5(4chlorophenyl)1,3,4oxadiazol2yl](nitroheteroaryl)carboxamides. Heterocyclic Communications. 2019;25(1): 52-599.
7. De SS, Khambete MP, Degani MS. Oxadiazole scaffolds in anti-tuberculosis drug discovery. Bioorganic & medicinal chemistry letters. 2019 Aug 15;29(16):1999-2007.
8. Mei WW, Ji SS, Xiao W, Wang XD, Jiang CS, Ma WQ, Zhang HY, Gong JX, Guo YW. Synthesis and biological evaluation of benzothiazol-based 1, 3, 4-oxadiazole derivatives as amyloid β-targeted compounds against Alzheimer’s disease. Monatshefte für Chemie-Chemical Monthly. 2017 Oct;148:1807-15.
9. Arica-Sosa A, Alcántara R, Jiménez-Avalos G, Zimic M, Milón P, Quiliano M. Identifying RO9021 as a Potential Inhibitor of PknG from Mycobacterium tuberculosis: combinative computational and in vitro studies. ACS omega. 2022 May 31;7(23):20204-18.
10. Patel NB, Patel JC. Synthesis and Antimicrobial Activ-ity of 3-(1, 3, 4-Oxadiazol-2-yl) quinazolin-4 (3H)-ones. Scientia pharmaceutica. 2010 Jun;78(2):171-94
11. Singh N, Tiwari S, Srivastava KK, Siddiqi MI. Identifi-cation of novel inhibitors of Mycobacterium tubercu-losis PknG using pharmacophore based virtual screening, docking, molecular dynamics simulation, and their biological evaluation. Journal of chemical information and modeling. 2015 Jun 22;55(6):1120-9.
12. Khan MZ, Bhaskar A, Upadhyay S, Kumari P, Rajmani RS, Jain P, Singh A, Kumar D, Bhavesh NS, Nandicoori VK. Protein kinase G confers survival advantage to Mycobacterium tuberculosis during latency-like con-ditions. Journal of Biological Chemistry. 2017 Sep 29;292(39):16093-108
13. Santhi N, Aishwarya S. Insights from the molecular docking of withanolide derivatives to the target pro-tein PknG from Mycobacterium tuberculosis. Bioin-formation. 2011;7(1):1
14. Abdullahi M, Adeniji SE. In-silico molecular docking and ADME/pharmacokinetic prediction studies of some novel carboxamide derivatives as anti-tubercular agents. Chemistry Africa. 2020 Dec;3(4):989-1000.
15. Sonia G, Ravi TK. Design, synthesis and antitubercular screening of certain novel thiadiazolyl pyrrolidine carboxamides as enoyl acp reductase inhibitors. Int J Pharm Pharm Sci. 2011;3(4):280-4
16. Abdullahi M, Adeniji SE, Arthur DE, Musa S. Quantitative structure-activity relationship (QSAR) modelling study of some novel carboxamide series as new anti-tubercular agents. Bulletin of the National Research Centre. 2020 Aug 18;44(1):136.
17. Ray R, Birangal SR, Fathima F, Boshoff HI, Forbes HE, Hariharapura RC, Shenoy GG. Molecular insights into Mmpl3 lead to the development of novel indole-2-carboxamides as antitubercular agents. Molecular systems design & engineering. 2022;7(6):592-606.
18. Canche Chay CI, Gomez Cansino R, Espitia Pinzon CI, Torres-Ochoa RO, Martínez R. Synthesis and anti-tuberculosis activity of the marine natural product caulerpin and its analogues. Marine drugs. 2014 Mar 27;12(4):1757-72.
19. Wang J, Ge P, Lei Z, Lu Z, Qiang L, Chai Q, Zhang Y, Zhao D, Li B, Su J, Peng R. Mycobacterium tuberculosis protein kinase G acts as an unusual ubiquitinating enzyme to impair host immunity. EMBO reports. 2021 Jun 4;22(6):e52175.
20. Akhter M, Husain A, Azad B, Ajmal M. Aroylpropionic acid based 2, 5-disubstituted-1, 3, 4-oxadiazoles: Synthesis and their anti-inflammatory and analgesic activities. European Journal of Medicinal Chemistry. 2009 Jun 1;44(6):2372-8.
21. Tok F, Kocyigit‐Kaymakcioglu B, Tabanca N, Estep AS, Gross AD, Geldenhuys WJ, Becnel JJ, Bloomquist JR. Synthesis and structure–activity relationships of car-bohydrazides and 1, 3, 4‐oxadiazole derivatives bearing an imidazolidine moiety against the yellow fever and dengue vector, Aedes aegypti. Pest management science. 2018 Feb;74(2):413-21.
Published
17/05/2024
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Chukka, A. K., C. Sireesha, L. S. M, D. C. M, H. S. M, I. Sk, and N. K. J. “In-Silico Predictive Binding Affinity and ADMET of Novel N-[5-(2-Fluorophenyl)-1, 3, 4-Oxadiazole-Carboxamide Derivatives towards Prot”. International Journal of Pharmacognosy and Chemistry, Vol. 5, no. 2, May 2024, pp. 1-6, doi:10.46796/ijpc.v5i2.584.
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