Design, synthesis and biological evaluation of a novel platinum(Ⅱ)complex possessing bioreductive groups for cancer therapy  

作　　者：Chengken Chen Chunmei Gao Zigao Yuan Yuyang Jiang 

机构地区：[1]Department of Chemistry, Tsinghua University [2]The Ministry-Province Jointly Constructed Base for State Key Lab-Shenzhen Key Laboratory of Chemical Biology, The Graduate School at Shenzhen, Tsinghua University [3]College of Chemistry and Chemical Engineering, Shenzhen University [4]Shenzhen Kivita Innovative Drug Discovery Institute [5]Department of Pharmacology and Pharmaceutical Sciences, School of Medicine, Tsinghua University

出　　处：《Chinese Chemical Letters》2019年第1期243-246,共4页中国化学快报（英文版）

基　　金：Shenzhen Sci & Tech Bureau (Nos. JCYJ20160301153959476 and JCYJ20160324163734374)

摘　　要：Cisplatin is one of the most successful antitumor agents, yet also restricted by its poor cellular uptake and low selectivity. Since 3-(2-nitrophenyl) propionic acid(NPPA) has been reported as a bioreductive prodrug moiety, herein we combined NPPA with cisplatin(compound 1) to improve its lipophilicity and targetability and then to improve the antitumor outcomes. In addition, compound 2 possessing 3-phenyl propionic acid(PPA) was also synthesized as a comparison to test the influence of the NPPA to the cytotoxicity, since PPA was not a bioreductive moiety. Bioevaluations showed that 1 displayed more potent antitumor potency than cisplatin and 2, suggesting Pt(II) complexes possessing NPPA groups may be a good strategy for future platinum drug discovery.Cisplatin is one of the most successful antitumor agents, yet also restricted by its poor cellular uptake and low selectivity. Since 3-(2-nitrophenyl) propionic acid(NPPA) has been reported as a bioreductive prodrug moiety, herein we combined NPPA with cisplatin(compound 1) to improve its lipophilicity and targetability and then to improve the antitumor outcomes. In addition, compound 2 possessing 3-phenyl propionic acid(PPA) was also synthesized as a comparison to test the influence of the NPPA to the cytotoxicity, since PPA was not a bioreductive moiety. Bioevaluations showed that 1 displayed more potent antitumor potency than cisplatin and 2, suggesting Pt(II) complexes possessing NPPA groups may be a good strategy for future platinum drug discovery.

关 键 词：PLATINUM COMPOUNDS Bioreductive Nitrophenylalkanoic GROUP CELLULAR UPTAKE ANTITUMOR 

分 类 号：O6[理学—化学]