engleski

Proapoptotic potential of novel N-9-sulfonylpurine-6-amine derivatives on tumor cells in vitro

Novel of N-9-sulfonylpurine-6-amine derivatives with purine scaffold are synthesized to behave as antimetabolites and promote cytotoxicity in tumor cells. Antiproliferative potential of N-9-sulfonylpurine-6-amine derivatives were determined by MTT test on human tumor cells with different histological origin such as carcinoma cells (HeLa, CaCo-2 and NCI-H358), leukemia cells (K562, CCRF-CEM and MOLT4), lymphoma cells (Raji and HuT-78), and normal cell lines (BJ and MDCK1). Derivative with styryl group linked to purine scaffold via sulfonyl group displayed the best antiproliferative effect. Therefore, further investigation of cell death mechanism was focused on derivative with styryl group. Membrane integrity, as an indicator of cytotoxicity was determined after 3, 6, 10 and 24 h by LDH assay. Flow cytometry was used to determine apoptosis, mitochondrial potential and accumulation of ROS in cells. Catalytic activity of caspase 3 was determined by colorimetric assay after 24h of treatment. Meaningful reduction in cellular growth by N-9-sulfonylpurine-6-amine derivatives is apparent in leukemia and lymphoma cells, with decreased influence on carcinoma cells. One of the derivative with styril group promotes cytotoxicity through activation of apoptosis accompanied with impaired mitochondrial potential in >70% of treated cells with increased ROS accumulation. Cell membrane is disrupted after 6h, with 20-60% of LDH released from cells. There is no apparent increase in caspase 3 activity. Tested N-9-sulfonylpurine-6-amine derivatives have proven to be good candidates for further antitumor’s studies.

sulfonylpurine derivatives ; cell lines ; apoptosis

nije evidentirano