title: New water-soluble palladium(II) complexes of lidocaine and phenylcyanamide derivative ligands: cytotoxicity and cellular response mechanisms.
abstract: Three new palladium(II) complexes of lidocaine and phenylcyanamide derivative ligands of formula K[Pd(2,6-Me2pcyd)2(LC)], 1, K[Pd(2,6-Et2pcyd)2(LC)], 2, K[Pd(2,6-Cl2pcyd)2(LC)], 3 (LC: lidocaine, 2,6-Me2pcyd: 2,6-dimethyl phenylcyanamide, 2,6-Et2pcyd: 2,6-diethyl phenylcyanamide, 2,6-Cl2pcyd: 2,6-dichloro phenylcyanamide) have been synthesized and fully characterized. The complexes 1-3 revealed a significant in vitro antiproliferative activity against human ovarian carcinoma (A2780), colorectal adenocarcinoma (HT29), breast (MCF-7), liver hepatocellular carcinoma (HepG-2) and lung adenocarcinoma (A549) cancer cell lines. All the complexes are more active than cisplatin and follow the trend 2 > 1 > 3. Mechanistic studies showed that the trend in cytotoxicity of the Pd(II) complexes is mainly consistent with their ability to accumulate into cancer cells and to increase intracellular basal reactive oxygen species levels, which consequently results in the loss of mitochondrial membrane potential and apoptosis induction.
authors.affiliation: Department of Chemistry, Isfahan University of Technology, Isfahan, 84156-83111, Iran. tabrizi79@gmail.com.
authors.forename: Leila
authors.initials: L
authors.lastname: Tabrizi
authors.affiliation: Department of Chemistry, Isfahan University of Technology, Isfahan, 84156-83111, Iran. Chinif@cc.iut.ac.ir.
authors.forename: Hossein
authors.initials: H
authors.lastname: Chiniforoshan
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D056831:Coordination Complexes / Q000737:chemistry / Q000494:pharmacology*; D003484:Cyanamide / Q000737:chemistry*; D006801:Humans; D008012:Lidocaine / Q000737:chemistry*; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology*; D010165:Palladium / Q000737:chemistry*; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D056831:Coordination Complexes; D003484:Cyanamide; D010165:Palladium; D008012:Lidocaine
keywords: Apoptosis; Cytotoxicity; Lidocaine; Pd(II) complex; Phenylcyanamide