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

TL;DR

This study evaluates new purine compounds for treating aggressive ovarian cancer, finding one that shows promise by stopping cancer cell growth and inducing cell death.

Contribution

The paper introduces novel 6,9-disubstituted purine analogues and identifies compound 8 as a potential therapeutic lead for HGSOC.

Findings

Compound 8 exhibited significant cytotoxic activity with low micromolar IC50 values in HGSOC cell lines.

Compound 8 may inhibit DNA replication and induce apoptosis in cancer cells.

The compound shows potential as a lead for developing new ovarian cancer treatments.

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.

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.

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.

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.

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