Novel [(3-indolylmethylene)hydrazono]indolin-2-ones As Apoptotic Anti-proliferative Agents: Design, Synthesis and in Vitro Biological Evaluation

Overview

Journal J Enzyme Inhib Med Chem

Specialty Biochemistry

Date 2018 Mar 22

PMID 29560733

Citations 24

Authors

Wagdy M Eldehna

Mahmoud F Abo-Ashour

Hany S Ibrahim

Ghada H Al-Ansary

Hazem A Ghabbour

Mahmoud M Elaasser

Hanaa Y A Ahmed

Nesreen A Safwat

Affiliations

Soon will be listed here.

Abstract

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=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.

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