title: New trans-platinum drugs with phosphines and amines as carrier ligands induce apoptosis in tumor cells resistant to cisplatin.
abstract: Cisplatin resistance observed in some human tumors has prompted research in platinum derivatives that can circumvent this effect. Despite initial works reporting lack of activity of trans-platinum derivatives, complexes with 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 PMe2Ph in trans to several amines. They show important antitumoral properties in tumor cell lines. Among the compounds, those with a replacement of an ammine ligand in the inactive trans-DDP by a phosphine ligand have an important enhancement of their cytotoxic activity. In SKOV3, no G1 nor G2/M accumulation was observed after treatments, and apoptosis was launched probably by a mechanism independent of classical checkpoints activation. Our data indicate that our compounds are not cross-resistant with cisplatin and might be promising agents in the treatment of tumors unresponsive to cisplatin.
authors.affiliation: Departamento de Química InorgAnica, Universidad Autónoma de Madrid, 28049 Madrid, Spain.
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Ramos-Lima
authors.forename: Adoración G
authors.initials: AG
authors.lastname: Quiroga
authors.forename: Beatriz
authors.initials: B
authors.lastname: García-Serrelde
authors.forename: Fernando
authors.initials: F
authors.lastname: Blanco
authors.forename: Amancio
authors.initials: A
authors.lastname: Carnero
authors.forename: Carmen
authors.initials: C
authors.lastname: Navarro-Ranninger
mesh_terms: D000588:Amines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis; D002455:Cell Division; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor; D016195:G2 Phase; D006801:Humans; D008024:Ligands; D009944:Organoplatinum Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D010720:Phosphines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D000588:Amines; D000970:Antineoplastic Agents; D008024:Ligands; D009944:Organoplatinum Compounds; D010720:Phosphines; D002945:Cisplatin