Biological Evaluation of Novel Structure-Activity Platinum Complexes
Shaohua Gou
Pharmaceutical Research Center, School of Chemistry & Chemical Engineering, Southeast University, Nanjing 211189
Abstract:
A number of N-substituted azetidine-3,3-dicarboxylato derivatives have been designed and prepared as ligands. Their corresponding platinum (II) complexes with ammonia or trans-1R, 2R-diaminocyclohexane were formed in an unexpected N-O coordination mode. X-ray crystal structures of several platinum complexes indicated that the metal atom, in a square planar geometry, is four-coordinated by one N atom and one O atom of a carboxylate anion from the ligand in addition to two N atoms from amines. Biological evaluation showed that one of these complexes exhibited a potent antitumor effect comparable to cisplatin and oxaliplatin in vitro, and lower toxicity than carboplatin in vivo. By comparing the structure-effect relationship of the complexes, we found that when the tertiary nitrogen atom of the N-substituted azetidine-3, 3-dicarboxylato ligand was linked with an m-methoxybenzyl group, the corresponding complex displayed better activity. In view of these facts, the complexes may have different mechanism from the classical structure-activity platinum complexes, which need to be clarified in the further investigation.
