Purine derivatives with heterocyclic moieties and related analogues as new antitiumour agents

Aim: Identification of new antiproliferative compounds. Methodology: Four series of compounds were synthesized by the Mitsunobu reaction. Their antiproliferative activity was studied against several cancer cells and a non-cancerous fibroblast cell line. Their apoptotic activity was analyzed using a caspase 3/7 fluorescence assay. Results & Conclusion: 9-Alkylated-6-halogenated and 2,6-dihalogenated purines show remarkable inhibition of tumour cell proliferation, with the dichloro derivatives being the most potent of all the series. The most promising compound, tetrahydroquinoline 4c, exhibits significant antiproliferative activity against the cancer cells tested, while displaying a 19-fold lower potency against non-cancerous fibroblasts, a key feature that indicates potential selectivity against cancer cells. This compound produces a high percentage of apoptosis (58%) after 24h treatment in the human breast cancer MCF-7 cells.