Synthesis of novel N-9 substituted 6-(4-(4-propoxyphenyl)piperazin-1-yl)-9H-purine derivatives as inducers of apoptosis in MCF-7 breast cancer cells

Abstract

A series of N-9 substituted 6-(4-(4-propoxyphenyl)piperazin-1-yl)-9H-purine derivatives (PP05–PP21) were prepared and evaluated for their anticancer activity against a panel of human cancer cell lines. Evaluation of results revealed that some of the synthesized compounds exhibited promising anticancer activity against the examined cancer cell lines. The structure–activity relationship (SAR) studies in the present work revealed that simple N-9 alkyl substituted 6-(4-(4-propoxyphenyl)piperazin-1-yl)-9H-purines are potent anticancer agents. Among all the compounds, PP17 (9-sec-butyl-6-(4-(4-propoxyphenyl)piperazin-1-yl)-9H-purine) showed good inhibitory activity against MCF-7 cells. Cell cycle analysis of the compound suggested that induces G2/M phase arrest. Biochemical experiments showed that PP17 significantly induced MCF-7 cell apoptosis. Therefore, compound PP17 with a potent in vitro anticancer activity can serve as a promising lead compound for further study.