Structure-activity relationship of [1,5]azastibocines in cytotoxicity to vascular endothelial cells

It has been well established that organic-inorganic hybrid molecules can exhibit biological activities that are different from those of either their intramolecular metals in inorganic forms or their organic structures. We have previously reported that organoantimony compound Sb-phenyl-N-methyl-5, 6,7,12-tetrahydrodibenz[c,f][1,5]azastibocine (PMTAS) is nontoxic, but that the compound exhibits cytotoxicity in vascular endothelial cells when the antimony atom is replaced with a bismuth atom. In the present study, we investigated the cytotoxicity and intracellular accumulation of PMTAS and its analogs and found that the cytotoxicity of PMTAS analogs also decrease depending on the electron-withdrawing property of the substituent bound to the intramolecular antimony atom. On the other hand, with the exception of the phenyl group, and depending on the carbon number of hydrocarbon group bound to the intramolecular nitrogen atom, cytotoxicity was enhanced. Furthermore, the cytotoxicity of PMTAS analogs correlated with their intracellular accumulation values. These results suggested that the low cytotoxicity effects of PMTAS on vascular endothelial cells is due to the characteristics of substituents bound to intramolecular antimony and nitrogen atoms.