Synthesis and biological evaluation of novel 4,7-dihydroxycoumarin derivatives as anticancer agents

[Display omitted] A series of novel 4,7-dihydroxycoumarin based acryloylcyanohydrazone derivatives were synthesized and evaluated for antiproliferative activity against four different cancer cell lines (A549, HeLa, SKNSH, and MCF7). Most of the compounds displayed potent cytotoxicity with IC50 value...

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Bibliographic Details
Published in:Bioorganic & medicinal chemistry letters 2019-07, Vol.29 (14), p.1819-1824
Main Authors: Govindaiah, Pilli, Dumala, Naresh, Grover, Paramjit, Jaya Prakash, M.
Format: Article
Language:English
Subjects:
4,7-Dihydoxycoumarin
Acryloylcyanohydrazone
Anticancer
Cell cycle
Molecular docking
Tubulin
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Summary:[Display omitted] A series of novel 4,7-dihydroxycoumarin based acryloylcyanohydrazone derivatives were synthesized and evaluated for antiproliferative activity against four different cancer cell lines (A549, HeLa, SKNSH, and MCF7). Most of the compounds displayed potent cytotoxicity with IC50 values ranging from 3.42 to 31.28 µM against all the tested cancer cell lines. The most active compound, 8h was evaluated for pharmacological mechanistic studies on cell cycle progression and tubulin polymerization inhibition assay. The results revealed that the compound 8h induced the cell cycle arrest at G2/M phase and inhibited tubulin polymerization with IC50 = 6.19 µM. Experimental data of the tubulin polymerization inhibition assay was validated by molecular docking technique and the results exhibited strong hydrogen bonding interactions with amino acids (ASN-101, TYR-224, ASN-228, LYS-254) of tubulin.
ISSN:0960-894X
1464-3405
DOI:10.1016/j.bmcl.2019.05.008