Synthesis, antiproliferative and mitochondrial impairment activities of bis-alkyl-amino transplatinum complexes

• Published in: Bioorganic & medicinal chemistry Vol. 21; no. 22; pp. 6965 - 6972
• Main Authors: Dalla Via, Lisa, García-Argáez, Aída N., Adami, Arianna, Grancara, Silvia, Martinis, Pamela, Toninello, Antonio, Belli Dell’Amico, Daniela, Labella, Luca, Samaritani, Simona
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 15-11-2013
• Subjects: Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Antiproliferative activity; Apoptosis - drug effects; Cell Line, Tumor; Cell Proliferation - drug effects; Coordination Complexes - chemical synthesis; Coordination Complexes - chemistry; Coordination Complexes - pharmacology; HeLa Cells; Humans; Isomerism; Membrane Potential, Mitochondrial - drug effects; Mitochondria; Mitochondria - drug effects; Mitochondria - metabolism; Mitochondrial permeability transition; Oxidative stress; Phosphines - chemistry; Platinum - chemistry; Platinum - pharmacology; Transplatinum complexes; Oxidative stress; Mitochondria; Mitochondrial permeability transition; Antiproliferative activity; Transplatinum complexes
• ISSN: 0968-0896; 1464-3391
• DOI: 10.1016/j.bmc.2013.09.025

A convenient synthetic route and the characterization of complexes trans-[PtCl2(L)(PPh3)] (L=Et2NH (2), (PhCH2)2NH (3), (HOCH2CH2)2NH) (4) are reported. The antiproliferative activity was evaluated on three human tumor cell lines. The investigation on the mechanism of action highlighted for the most active complex 4 the capacity to affect mitochondrial functions. In particular, both the induction of the mitochondrial permeability transition phenomenon and an aspecific membrane damage occurred, depending on concentration.