Biological evaluation of novel 6,9-disubstituted purine analogues in high-grade serous ovarian cancer cell lines

Abstract

High-grade serous ovarian cancer (HGSOC) remains one of the most aggressive forms of ovarian malignancy and frequently shows resistance to conventional therapies. This study aimed to synthesize a novel series of purine analogues, 6-[(4-substituted benzyl amine)/(4-substituted aniline)]-9-cyclopentyl purines, and evaluate their anticancer efficacy against HGSOC cell lines. Materials and methods: We assessed the biological effects of the synthesized purine analogues on the OVCAR3, OVSAHO, and KURAMOCHI HGSOC cell lines using the sulforhodamine B assay. To investigate the mechanism of action, we conducted flow cytometry and western blot analyses, focusing on DNA replication and apoptosis. Results: Among the tested compounds, compound 8 showed significant cytotoxic activity with IC50 values in the low micromolar range. Preliminary data from flow cytometry and western blot analyses indicated that compound 8 may inhibit DNA replication and induce apoptosis, as reflected by changes in cell viability and cell-cycle progression. Conclusion: Compound 8 may disrupt key proliferative mechanisms in cancer cells by interfering with DNA synthesis and activating programmed cell death pathways. These findings suggest that compound 8 is a promising lead candidate for further development in ovarian cancer therapeutics.