Possible Binding Mode Analysis of Pyrazolo-triazole Hybrids as Potential Anticancer Agents through Validated Molecular Docking and 3D-QSAR Modeling Approaches

Title:Possible Binding Mode Analysis of Pyrazolo-triazole Hybrids as Potential Anticancer Agents through Validated Molecular Docking and 3D-QSAR Modeling Approaches

Volume: 14 Issue: 5

Author(s): Siekh Abdul Amin, Nilanjan Adhikari, Ram K. Agrawal, Tarun Jha*Shovanlal Gayen*

Affiliation:

• Department of Pharmaceutical Technology, P.O. Box 17020, Jadavpur University, Kolkata, 700032, WB,India

• Laboratory of Drug Design and Discovery, Department of Pharmaceutical Sciences, Dr. Harisingh Gour University (A Central University), Sagar 470003, MP,India

Keywords: ADMET, anticancer agents, druggability prediction, k-Nearest neighbor molecular field analysis, molecular docking, pyrazolo-triazole hybrids.

Abstract: Background: There has been a growing interest of pharmacophore hybridization in anticancer drug discovery that may be utilized for designing new potential lead candidates against multiple targets that may exhibit synergetic activity. Pyrazole and 1,2,3-triazole nucleus are amongst the most important ones.

Method: Statistically validated 3D-QSAR models of the pyrazolo-triazole hybrids on 4 different types of human cancer cell lines (U87MG, PC-3, HT-29 and A549) are constructed through simulated annealing k-Nearest neighbor molecular field analysis (SA-kNN-MFA) method followed by robust molecular docking study, druggability assessment and in silico ADMET analysis.

Results: 3D-QSAR study reveales the importance of electronegative group at R1 position and 3, 4- OCH3 substituent at R2 position that may enhance biological potency against these cancer cell lines. The docking analysis suggests that the pyrazolo-triazole hybrids may have better binding affinities compared to the redocked co-crystallized ligand for targets namely CDK-2, CDK-5, FTase, HSP-90, TGF-β, topoisomerase-I and tubulin. Moreover, these compounds show better ADMET profile than the standard drug 5-fluorouracil.

Conclusion: The results of molecular docking, druggability and ADMET analysis may focus the utility of targeting these possible potential enzymes for developing newer pyrazolo-triazoles as multi-targeted anticancer agents.

Cite this article as:

Amin Abdul Siekh, Adhikari Nilanjan, Agrawal K. Ram, Jha Tarun*, Gayen Shovanlal*, Possible Binding Mode Analysis of Pyrazolo-triazole Hybrids as Potential Anticancer Agents through Validated Molecular Docking and 3D-QSAR Modeling Approaches, Letters in Drug Design & Discovery 2017; 14 (5) . https://dx.doi.org/10.2174/1570180813666160916153017

DOI https://dx.doi.org/10.2174/1570180813666160916153017	Print ISSN 1570-1808
Publisher Name Bentham Science Publisher	Online ISSN 1875-628X