@article{79760db2c97c404dae9eacc0abbe2a91,
title = "Design and Synthesis of New Tubulin Polymerization Inhibitors Inspired from Combretastatin A-4: An Anticancer Agent",
abstract = "A series of 30 small hybrid molecules are synthesized inspired from Combretastatin A-4 (CA-4), where ethylene-bridge of CA-4 is replaced with two five-membered heterocyclic rings, viz. isoxazoline and 1, 2, 3-triazole. These are joined by a methylene linker, with substitutions at A and B – ring position of CA-4. The new molecular entities have shown significant cytotoxicity to cancer cell from the IC50 0.49 μM–3.17 μM with 1-((4,5-Dihydro-3-(2,5-dimethoxyphenyl)isoxazol-5-yl)methyl)-4-(4-methoxyphenyl)-1H-1,2,3-triazole displayed IC50 0.422±0.07 μM for A-549 -lung cancer cell line and IC50 0.498±0.03 μM for MDA-MB-231-breast cancer cell line. The western blot analysis, confocal staining and also by in vitro tubulin polymerization assay established the target specificity of the molecules as a tubulin polymerization inhibitor. Molecular docking & Molecular dynamics studies confirmed the binding interaction patterns of these molecules at the Colchicine binding site of tubulin and have correlated the observed experimental result with variation in structure satisfactorily.",
keywords = "Cancer, Click Chemistry, Colchicine binding site, Combretastatin A-4, Medicinal Chemistry",
author = "Akanksha Sharma and Doddabasappa Talimarada and Yadav, {Umesh Prasad} and Nidhi Singh and Reddy, {A. Sudharshan} and Debojyoti Bag and Krishna Biswas and Amit Baidya and Borale, {Asha N.} and Dhananjay Shinde and Sandeep Singh and Harish Holla",
note = "Funding Information: The author would like to acknowledge NCBS, Bangalore for recording HRMS. The author is sincerely thankful to Dr. Pritesh Bhat from Schr{\"o}dinger Inc. for critical advises provided on molecular modelling study. The authors thank DST-SERB, New Delhi, for partial financial assistance with grant SB/S1/OC-76/2013. Authors are thankful to Hon'ble Vice-Chancellor, Central University of Karnataka, Kalaburagi & Central University of Punjab, Bathinda for providing required facility to conduct the work. Akanksha Sharma is thankful to Central University of Karnataka for research fellowship. Umesh Prasad Yadav thank CSIR-Grant-NO-09/1051 (0009)/2017, for providing Junior Research Fellowship Funding Information: The author would like to acknowledge NCBS, Bangalore for recording HRMS. The author is sincerely thankful to Dr. Pritesh Bhat from Schr{\"o}dinger Inc. for critical advises provided on molecular modelling study. The authors thank DST‐SERB, New Delhi, for partial financial assistance with grant SB/S1/OC‐76/2013. Authors are thankful to Hon'ble Vice‐Chancellor, Central University of Karnataka, Kalaburagi & Central University of Punjab, Bathinda for providing required facility to conduct the work. Akanksha Sharma is thankful to Central University of Karnataka for research fellowship. Umesh Prasad Yadav thank CSIR‐Grant‐NO‐09/1051 (0009)/2017, for providing Junior Research Fellowship Publisher Copyright: {\textcopyright} 2020 Wiley-VCH GmbH",
year = "2020",
month = oct,
day = "8",
doi = "10.1002/slct.202003170",
language = "English (US)",
volume = "5",
pages = "11560--11572",
journal = "ChemistrySelect",
issn = "2365-6549",
publisher = "Wiley-Blackwell Publishing Ltd",
number = "37",
}