Cytotoxicity and cellular response mechanisms of water-soluble platinum(II) complexes of lidocaine and phenylcyanamide derivatives

摘要: Three new platinum(II) complexes of lidocaine and phenylcyanamide derivative ligands formula K[Pt(3,5-(NO2)2pcyd)2(LC)], 1, K[Pt(3,5-(CF3)2pcyd)2(LC)], 2, K[Pt(3,5-Cl2pcyd)2(LC)], 3 (LC: lidocaine, 3,5-(NO2)2pcyd: 3,5-dinitro phenylcyanamide, 3,5-(CF3)2pcyd: 3,5-bis(trifluoromethyl) 3,5-Cl2pcyd: 3,5-dichloro phenylcyanamide) have been synthesized fully characterized. Cellular uptake, DNA platination cytotoxicity against a panel human tumor cell lines were evaluated. The 1–3 revealed significant in vitro antiproliferative activity ovarian carcinoma (A2780), colorectal adenocarcinoma (HT29), breast (MCF-7), liver hepatocellular (HepG-2) lung (A549) cancer lines. All the are more active than cisplatin follow trend 1 > 2 > 3. Mechanistic studies showed that Pt(II) is mainly consistent with their ability to accumulate into cells increase intracellular basal reactive oxygen species levels, which consequently results loss mitochondrial membrane potential apoptosis induction. complex 1 caused approximately 80-fold higher level respect cisplatin. can considerably stimulate production hydrogen peroxide time-dependent manner. Also, induced an (ROS) was superior by antimycin. had most effect on ROS comparison other complexes.