Synthesis, characterization, and biological activity of sterically hindered fluorine-containing platinum(II) complexes

Abstract

Picoplatin is a sterically hindered antitumor compound with unique chemical and DNA binding properties, but its curative effect is not as good as other platinum drugs. Therefore, a series of sterically hindered fluorine-containing platinum(II) complexes Y1–Y5 were synthesized and characterized by introducing fluorine atoms at the 2-position of the pyridine group and different leaving group ligands. In vitro antiproliferative activity assessments of these complexes have been performed against A549, MCF-7, SW480, HCT116, HepG2 human cancer cell lines, and LO2 normal cells. The results showed that Y1 with 2-fluoropyridine coordination and chloride ion as the leaving group exhibited stronger antiproliferative activity and selectivity in the tested cancer cell lines, especially for A549 cancer cells. DNA binding constants were determined by UV absorption and fluorescence titration, and the binding ability of Y1 to DNA is much stronger than that of the others, which shows Y1 has better DNA damage ability. For the determination of apoptosis by the complex, the results were consistent with those of the MTT assay, and the apoptosis rate of Y1 reached 38.9%. Therefore, our work offers an advantageous method for the development of new platinum-based antitumor drugs.