Design, synthesis and biological evaluation of a novel platinum(II) complex possessing bioreductive groups for cancer therapy

Abstract Cisplatin is one of the most successful antitumor agents, yet also restricted by its poor cellular uptake and low selectivity. Since 3-(2-nitrophenyl) propionic acid (NPPA) has been reported as a bioreductive prodrug moiety, herein we combined NPPA with cisplatin (compound 1 ) to improve its lipophilicity and targetability and then to improve the antitumor outcomes. In addition, compound 2 possessing 3-phenyl propionic acid (PPA) was also synthesized as a comparison to test the influence of the NPPA to the cytotoxicity, since PPA was not a bioreductive moiety. Bioevaluations showed that 1 displayed more potent antitumor potency than cisplatin and 2 , suggesting Pt(II) complexes possessing NPPA groups may be a good strategy for future platinum drug discovery.