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Design, Synthesis and Pharmacological Evaluation of 4‐Hydroxycoumarin Derivatives as Antiproliferative Agents.
Author(s) -
Pilli Govindaiah,
Dumala Naresh,
Sreeja Jamuna S.,
John Rince,
Sengupta Suparna,
Grover Paramjit,
Prakash M. Jaya
Publication year - 2019
Publication title -
chemistryselect
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.437
H-Index - 34
ISSN - 2365-6549
DOI - 10.1002/slct.201902089
Subject(s) - hela , tubulin , chemistry , cell cycle , mtt assay , in vitro , docking (animal) , cell cycle checkpoint , cell culture , in silico , microtubule , stereochemistry , cell , biochemistry , biology , microbiology and biotechnology , medicine , genetics , nursing , gene
A series of novel 4‐hydroxycoumarin based acryloylcyanohydrazone derivatives were synthesized and evaluated for in vitro antiproliferative activity against different cancer cell lines (A‐549, HeLa, SK−N‐SH, and MCF‐7) by MTT assay method. All the test compounds ( 8 a‐m ) were exhibited excellent antiproliferative activity (IC 50 values ranging between 8.20 to 27.39 μM) against all the tested cancer cell lines. Pharmacological studies like cell cycle progression arrest and tubulin polymerisation inhibition studies were performed for the most potent compound 8 j . Further these studies were confirmed that the compound 8 j induced the cell cycle arrest at G2/M phase and tubulin polymerisation was inhibited with IC 50 =11.03 μM. Molecular docking simulation for the compound 8 j also revealed that, it has strong binding interactions towards tubulin protein. This in silico target validation suggested the tubulin is the target for the designed potent compound 8 j .