title: Synthesis, characterization and antiproliferative activity on mesothelioma cell lines of bis(carboxylato)platinum(IV) complexes based on picoplatin.
abstract: The synthesis and characterization of a series of picoplatin-based (picoplatin = [PtCl(2)(mpy)(NH(3))], mpy = 2-methylpyridine), Pt(iv) complexes with axial carboxylato ligands of increasing length are reported. The synthesis is based on the oxidation with hydrogen peroxide of picoplatin to give the cis,cis,trans-[PtCl(2)(mpy)(NH(3))(OH)(2)] intermediate and then its transformation into the dicarboxylato complexes cis,cis,trans-[PtCl(2)(mpy)(NH(3))(RCOO)(2)] (R = CH(3)(CH(2))(n), n = 0-4) with the corresponding anhydride. Pt(iv) complexes with n = 0-2 were selected to be tested on four malignant pleural mesothelioma (MPM) cell lines, on human mesothelial cells (HMC), and on the cisplatin-sensitive ovarian A2780 cell line along with cisplatin as a metallo-drug reference. In general, the longer the axial chain, the more cytotoxic and selective the Pt(IV) complex is. Pt(IV) analogs show good activity on the MPM cell lines, approaching or in some case bypassing that of cisplatin and represent quite promising drug candidates for the treatment of tumors whose chemoresistance is mainly based on glutathione overexpression, such as MPM.
authors.affiliation: Dipartimento di Scienze dell'Ambiente e della Vita, Università del Piemonte Orientale Amedeo Avogadro, Alessandria, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Ravera
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Gabano
authors.forename: Ilaria
authors.initials: I
authors.lastname: Zanellato
authors.forename: Ilaria
authors.initials: I
authors.lastname: Bonarrigo
authors.forename: Esther
authors.initials: E
authors.lastname: Escribano
authors.forename: Virtudes
authors.initials: V
authors.lastname: Moreno
authors.forename: Mercè
authors.initials: M
authors.lastname: Font-Bardia
authors.forename: Teresa
authors.initials: T
authors.lastname: Calvet
authors.forename: Domenico
authors.initials: D
authors.lastname: Osella
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002945:Cisplatin; D019008:Drug Resistance, Neoplasm; D005978:Glutathione; D006801:Humans; D008654:Mesothelioma / Q000188:drug therapy* / Q000473:pathology; D009944:Organoplatinum Compounds / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; C110525:amminedichloro(2-methylpyridine)platinum(II); D005978:Glutathione; D002945:Cisplatin