New trans-Platinum Drugs with Phosphines and Amines as Carrier Ligands Induce Apoptosis in Tumor Cells Resistant to Cisplatin

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• 作者：Francisco J. Ramos-Lima ; Adoració ; n G. Quiroga ; Beatriz Garcí ; a-Serrelde ; Fernando Blanco ; Amancio Carnero ; Carmen Navarro-Ranninger
• 刊名：Journal of Medicinal Chemistry
• 出版年：2007
• 出版时间：May 3, 2007
• 年：2007
• 卷：50
• 期：9
• 页码：2194 - 2199
• 全文大小：203K
• 年卷期：v.50,no.9(May 3, 2007)
• ISSN：1520-4804

文摘

Cisplatin resistance observed in some human tumors has prompted research in platinum derivatives that cancircumvent this effect. Despite initial works reporting lack of activity of trans-platinum derivatives, complexeswith the general formula PtCl₂(L)(L') exhibit cytotoxic activity in cisplatin-sensitive and -resistant cell lines.Here we reported the chemical and biological properties of seven platinum complexes with PPh₃ or PMe₂Phin trans to several amines. They show important antitumoral properties in tumor cell lines. Among thecompounds, those with a replacement of an ammine ligand in the inactive trans-DDP by a phosphine ligandhave an important enhancement of their cytotoxic activity. In SKOV3, no G1 nor G2/M accumulation wasobserved after treatments, and apoptosis was launched probably by a mechanism independent of classicalcheckpoints activation. Our data indicate that our compounds are not cross-resistant with cisplatin and mightbe promising agents in the treatment of tumors unresponsive to cisplatin.