Anticancer cytotoxicity and nephrotoxicity of the new platinum (II) complexes containing diaminocyclohexane and glycolic acid.
Cisplatin is an important antineoplastic agent, but dose-limiting nephrotoxicity prevents potential efficacy. There is interest in developing new platinum agents that have less toxicity. We have synthesized novel platinum (II) coordination complexes containing diaminocyclohexane as carrier ligands, and glycolic acid as a leaving group. In this study, new platinum (II) complex compounds were evaluated for cytotoxicity on cancer cell lines and nephrotoxicity. The new platinum complexes have demonstrated high efficacy in the cytotoxicity against human ovarian adenocarcinoma cell lines (SKOV-3/NIH.OVCAR-3) and human prostate carcinoma cell lines (DU-145/PC-3). The cytotoxicity of these compounds against rabbit proximal renal tubular cells and human renal cortical tissues was determined by MTT assay, the [3H]-thymidine uptake and glucose consumption test, and found to be considerably less than those of cisplatin. Based on our results, these novel platinum compounds appear to be valuable lead compounds with high efficacy and low nephrotoxicity.
Rho
Young-Soo
YS
Department of Pharmacochemistry, College of Pharmacy, Kyung Hee University, Dongdaemun-Gu, Seoul, Korea.
Kim
Soon Ae
SA
Jung
Jee-Chang
JC
Shin
Chu-Chil
CC
Chang
Sung-Goo
SG
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002478:Cells, Cultured; D004396:Coloring Agents / Q000494:pharmacology; D003510:Cyclohexanes / Q000627:therapeutic use*; D004247:DNA / Q000378:metabolism; D005260:Female; D005947:Glucose / Q000378:metabolism; D006016:Glycolates / Q000627:therapeutic use*; D006801:Humans; D007672:Kidney Cortex / Q000187:drug effects; D008024:Ligands; D008297:Male; D008956:Models, Chemical; D010051:Ovarian Neoplasms / Q000188:drug therapy; D017671:Platinum Compounds / Q000627:therapeutic use*; D011471:Prostatic Neoplasms / Q000188:drug therapy; D011817:Rabbits; D013778:Tetrazolium Salts / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology; D013936:Thymidine / Q000493:pharmacokinetics; D013997:Time Factors; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D004396:Coloring Agents; D003510:Cyclohexanes; D006016:Glycolates; D008024:Ligands; D017671:Platinum Compounds; D013778:Tetrazolium Salts; D013844:Thiazoles; C031149:glycolic acid; D004247:DNA; C022616:thiazolyl blue; D005947:Glucose; D013936:Thymidine