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A Comprehension into Target Binding and Spatial Fingerprints of Noscapinoid Analogues as Inhibitors of Tubulin

Author(s):

Seema Mandavi, Renu Bhatt, Sant Kumar Verma, Laxmi Banjare, Amit Dubey, Suresh Thareja and Akhlesh Kumar Jain*   Pages 1 - 12 ( 12 )

Abstract:


Aim: The present research aims to insight into target binding and mapping of spatial fingerprints of noscapinoids as inhibitors of tubulin.

Background: Owing to its potential to interfere in microtubule dynamics in mitotic phase of cell cycle and selectively inducing apoptosis in cancer cells without affecting normal cells, noscapine and its synthetic analogues have been investigated by other research groups in different cell lines for their capability to use as anti-cancer agents.

Objective: The present study is focused on investigation of mode of binding of noscapinoids with tubulin, prediction of target binding affinities and mapping of their spatial fingerprints (shape and electrostatic).

Methods: Molecular docking assisted alignment based 3D-QSAR technique self organizing molecular field analysis (SOMFA) was used on a dataset (43 molecules) having inhibitory activity (IC50 = 1.2-250 ┬ÁM) against human lymphoblast (CEM) cell line.

Results: Key amino acid residues of target tubulin were mapped for the binding of most potent noscapine analogue (Compound 11) and compared with noscapine. Spatial fingerprints of noscapinoids for favorable tubulin inhibitory activity were generated as an outcome of 3D-QSAR analysis.

Conclusion: The generated spatial fingerprints of noscapinoids would be used for further pharmacophoric amendments of noscapine analogues to design and develop novel potent noscapine based anti-cancer agents.The present molecular modeling study will be helpful to medicinal chemist in understanding the structural features of noscapinoids for further designing and synthesis of target specific safer inhibitors of tubulin that may enter to drug development pipeline.

Keywords:

Anticancer agents, 3D-QSAR, Noscapine analogues, Molecular docking, Spatial fingerprints, Tubulin inhibitors

Affiliation:

Department of Biotechnology,Guru Ghasidas Central University, Bilaspur- 495 009 (C.G.), Department of Biotechnology,Guru Ghasidas Central University, Bilaspur- 495 009 (C.G.), School of Pharmaceutical Sciences, Guru Ghasidas Central University, Bilaspur- 495 009 (C.G.), School of Pharmaceutical Sciences, Guru Ghasidas Central University, Bilaspur- 495 009 (C.G.), Chhattisgarh Council of Science and Technology, Raipur-492 014 (C.G.), School of Pharmaceutical Sciences, Guru Ghasidas Central University, Bilaspur- 495 009 (C.G.), School of Pharmaceutical Sciences, Guru Ghasidas Central University, Bilaspur- 495 009 (C.G.)



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