Novel [(3-indolylmethylene)hydrazono]indolin-2-ones as apoptotic anti-proliferative agents: design, synthesis and in vitro biological evaluation

On account of their significance as apoptosis inducing agents, merging indole and 3-hydrazinoindolin-2-one scaffolds is a logic tactic for designing pro-apoptotic agents. Consequently, 27 hybrids (6a-r, 9a-f and 11a-c) were synthesised and evaluated for their cytotoxicity against MCF-7, HepG-2 and H...

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Bibliographic Details
Published in:Journal of enzyme inhibition and medicinal chemistry 2018-01, Vol.33 (1), p.686-700
Main Authors: Eldehna, Wagdy M., Abo-Ashour, Mahmoud F., Ibrahim, Hany S., Al-Ansary, Ghada H., Ghabbour, Hazem A., Elaasser, Mahmoud M., Ahmed, Hanaa Y. A., Safwat, Nesreen A.
Format: Article
Language:English
Subjects:
anticancer
apoptosis
Indole
oxidative stress
Research Paper
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Summary:On account of their significance as apoptosis inducing agents, merging indole and 3-hydrazinoindolin-2-one scaffolds is a logic tactic for designing pro-apoptotic agents. Consequently, 27 hybrids (6a-r, 9a-f and 11a-c) were synthesised and evaluated for their cytotoxicity against MCF-7, HepG-2 and HCT-116 cancer cell lines. SAR studies unravelled that N-propylindole derivatives were the most active compounds such as 6n (MCF-7; IC 50 =1.04 µM), which displayed a significant decrease of cell population in the G2/M phase and significant increase in the early and late apoptosis by 19-folds in Annexin-V-FTIC assay. Also, 6n increased the expression of caspase-3, caspase-9, cytochrome C and Bax and decreased the expression of Bcl-2. Moreover, compounds 6i, 6j, 6n and 6q generated ROS by significant increase in the level of SOD and depletion of the levels of CAT and GSH-Px in MCF-7.
ISSN:1475-6366
1475-6374
DOI:10.1080/14756366.2017.1421181