title: Water-soluble N-substituted iminodiacetato(1,2-diaminocyclohexane)-platinum(II) complexes as potential antitumor agents.
abstract: A series of water-soluble N-substituted iminodiacetato(1,2-diaminocyclohexane)-platinum(II) complexes (IDP) were synthesized and tested for chemical stability, antitumor activity, and toxicity. The results obtained suggest that these complexes are relatively stable for more than 48 h when dissolved in water or phosphate buffer. All complexes had good in vitro cytotoxicity and were not cross-resistant with cis-dichloro-diammineplatinum(II) (DDP) in a DDP-resistant cell line in vitro. When the complexes were administered as a single i.p. injection to C57BL/6 X DBA/2F1 (hereafter called B6D2F1) mice inoculated with L1210 leukemia cells, a significant increase in mean survival time was observed, but there were few long-term survivors. When the complexes were administered on Days 1, 5, and 9 after tumor inoculation, however, cure rates of 50 to 85% were obtained. The oncolytic activity of the IDP complexes against L1210 ascites appeared much greater than that of DDP. The IDP complexes also had good antitumor activity when administered i.p. on Days 1, 5, and 9 following i.p. inoculation of B16 melanoma to B6D2F1 mice. Five of the six IDP complexes had no significant nephrotoxicity (as evidenced by lack of elevated blood urea nitrogen levels). N-Benzyl-iminodiacetato(1,2-diaminocyclohexane)-platinum(II) resolved into three distinct peaks of UV-absorbing material that corresponded with three distinct peaks of platinum-containing material. The exact chemical identity of the active component of this mixture is currently under investigation. The results obtained to date, however, suggest that the N-substituted iminodiacetato(1,2-diaminocyclohexane)-platinum(II) complexes are good candidates for further developmental studies.
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000633:toxicity; D055598:Chemical Phenomena; D002621:Chemistry; D002945:Cisplatin / Q000494:pharmacology; D007928:Lethal Dose 50; D007939:Leukemia L1210 / Q000473:pathology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009944:Organoplatinum Compounds / Q000494:pharmacology*; D012995:Solubility; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D002945:Cisplatin