Antiproliferative Activity of PtII Complexes with Carboxylated Phosphanes in Chelated or Ring-Opened Forms

Antiproliferative Activity of PtII Complexes with Carboxylated Phosphanes in Chelated or Ring-Opened Forms:

Abstract

The biological activity of four cisplatin-like Pt–phosphane complexes, namely, cis-[PtCl₂(L)₂], L = PPh₃, P(Ph)₂(p-C₆H₄-COOH), P(Ph)₂(-CH₂CH₂-COOH) and its succinimidyl ester derivative, has been tested on monolayer cultures of three tumour cell lines (namely, A2780 human ovarian carcinoma and its cisplatin-resistant form A2780Cp8, and human colon adenocarcinoma HCT116). These complexes can undergo intramolecular rearrangements by virtue of their functionalized phosphanes, thereby existing as fully opened (O) or fully closed (C) forms. Our results show that only the opened forms exhibit moderate activity, which, although inferior to the activity exhibited by the archetype metallo-drug cisplatin, is substantially retained in the A2780Cp8 cell line, yielding very low resistance factors. The trend is also maintained on the less cisplatin-sensitive HCT116 line. When the complexes assume the bis-chelated (C) form, the antiproliferative activity is deeply reduced. Two Pt-amine congeners, containing β-alanine and 3-methoxypropylamine, with C and O structures, respectively, were synthesized and their antiproliferative propensity was evaluated for comparison purposes, and a similar scenario was observed.

The biological activity of four cisplatin-like Pt–phosphane complexes has been tested. Some of the complexes can undergo intramolecular rearrangement by virtue of the functionalized phosphanes (fully opened/fully closed forms). The results show that only the opened forms exhibit moderate activity, which is substantially retained in the cisplatin-resistant cell lines.