One-pot Three-component Synthesis of Novel Spirooxindoles with Potential Cytotoxic Activity Against Triple-negative Breast Cancer MDA-MB-231 Cells

Overview

Journal J Enzyme Inhib Med Chem

Specialty Biochemistry

Date 2017 Dec 29

PMID 29281924

Citations 23

Authors

Wagdy M Eldehna

Dina H El-Naggar

Ahmed R Hamed

Hany S Ibrahim

Hazem A Ghabbour

Hatem A Abdel-Aziz

Affiliations

Soon will be listed here.

Abstract

Triple-negative breast cancer (TNBC) is a highly aggressive malignancy with limited treatment options due to its heterogeneity and the lack of well-defined molecular targets. In our endeavour towards the development of novel anti-TNBC agents, herein we report a one-pot three-component synthesis of novel spirooxindoles 6a-p, and evaluation of their potential anti-proliferative activity towards TNBC MDA-MB-231 cells. Spirooxindoles 6a, 6e and 6i emerged as the most potent analogues with IC = 6.70, 6.40 and 6.70 µM, respectively. Compounds 6a and 6e induced apoptosis in MDA-MB-231 cells, as evidenced by the up-regulation of the Bax and down-regulation of the Bcl-2, besides boosting caspase-3 levels. Additionally, 6e displayed significant increase in the percent of annexin V-FITC positive apoptotic cells from 1.34 to 44%. Furthermore, spirooxindoles 6e and 6i displayed good inhibitory activity against EGFR (IC = 120 and 150 nM, respectively). Collectively, these data demonstrated that 6e might be a potential lead compound for the development of effective anti-TNBC agents.

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