Synthesis and biological evaluation of spiro[cyclopropane-1,3'-indolin]-2'-ones as potential anticancer agents

Bioorganic & Medicinal Chemistry Letters
Chada Narsimha ReddyAhmed Kamal

Abstract

Libraries of spiro[cyclopropane-1,3'-indolin]-2'-ones were synthesized and evaluated for their biological activity against five different human cancer cell lines HT-29 (colon cancer), DU-145 (prostate cancer), Hela (cervical cancer), A-549 (Lung cancer), and MCF-7 (breast cancer). Many compounds of the series exhibited promising anticancer activity (IC50<20 μM) against the studied cell lines. Based on the screening results, a structure activity relationship (SAR) of the pharmacophore was proposed. Among the series compound 6b and 6u showed significant activity against human prostate cancer cell line, DU-145. Flow cytometric analysis showed that these two compounds arrested the cell cycle in the G0/G1 phase leading to caspase-3 dependent apoptotic cell death. Further, measurement of mitochondrial membrane potential and Annexin V-FITC assay also suggested that 6b and 6u induced cell death by apoptosis.

References

Feb 3, 2000·Journal of the National Cancer Institute·P GiannakakouT Fojo
Jul 23, 2003·Trends in Pharmacological Sciences·Paula M ChecchiHarish C Joshi
Nov 4, 2006·Cell Death and Differentiation·S Kumar
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Citations

Aug 3, 2016·Molecular Diversity·Sagiv WeintraubArie Gruzman
Oct 8, 2016·Organic & Biomolecular Chemistry·K N Visweswara SastryAhmed Kamal
Dec 24, 2018·Organic & Biomolecular Chemistry·Haibo MeiJianlin Han
Feb 19, 2021·European Journal of Medicinal Chemistry·Darshana BoraNagula Shankaraiah

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