Allyl palladium complexes bearing carbohydrate‐based N‐heterocyclic carbenes: Anticancer agents for selective and potent in vitro cytotoxicity

Abstract

Novel allyl palladium compounds stabilized by carbohydrate‐based N‐heterocyclic carbenes (NHCs) were prepared and characterized by nuclear magnetic resonance, high‐resolution mass spectrometry and elemental analysis. The antiproliferative activity of the compounds was tested on a panel of different tumor lines, especially ovarian cancer and MRC‐5 human lung fibroblasts (nontumor cells). These experiments showed that both mixed NHC/PPh3 and NHC/PTA (PTA = 1,3,5‐triaza‐7‐phosphaadamantane) allyl complexes have IC50 (half maximal inhibitory concentration) values comparable and sometimes even significantly lower than cisplatin. Moreover, the mixed NHC/PTA allyl complexes exhibit good activity toward the seven tumor lines tested with a substantial inactivity against normal cells, a necessary condition to avoid the general cytotoxicity of a metallo‐drug. Furthermore, this subclass of compounds proved particularly active on the A549 lung cancer tumor line (up to 100‐fold more cytotoxic than cisplatin) and exhibited satisfactory cytotoxicity against KURAMOCHI and OVCAR3 cell lines, which are currently considered the best in vitro models for serous ovarian cancer, the most lethal tumor for women worldwide.