title: In vitro antitumour activity and cellular pharmacological properties of the platinum-iminoether complex trans-[PtCl2[E-HN=C(OMe)Me]2].
abstract: The platinum complex trans-[PtCl2¿E-HN=C(OMe)Me¿2] was compared to cisplatin for cytotoxicity towards tumour cells, and for cellular pharmacological properties in A2780 and cisplatin-resistant A2780/Cp8 ovarian cancer cells. Trans-[PtCl2¿E-HN=C(OMe)Me¿2] was comparably cytotoxic to cisplatin (mean IC50 after 72 h exposure = 6. 1 microM and 7 microM, respectively) and did not show cross-resistance in A2780/Cp8 cells (resistance factor = 0.9). Cellular accumulation measurements after treatment with equimolar drug concentrations showed that trans-[PtCl2¿E-HN=C(OMe)Me¿2] entered both A2780 and A2780/Cp8 cells much more efficiently than cisplatin, whose accumulation was reduced in A2780/Cp8 cells. Unlike cisplatin, trans-[PtCl2¿E-HN=C(OMe)Me¿2] induced rapidly cell death and cell cycle modifications of treated cells, thus indicating substantially different mechanistic properties.
authors.affiliation: Dipartimento Scienze Biomediche e Oncologia Umana, Universia di Bari, I-70124 Bari, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Coluccia
authors.forename: A
authors.initials: A
authors.lastname: Nassi
authors.forename: A
authors.initials: A
authors.lastname: Boccarelli
authors.forename: D
authors.initials: D
authors.lastname: Giordano
authors.forename: N
authors.initials: N
authors.lastname: Cardellicchio
authors.forename: F P
authors.initials: FP
authors.lastname: Intini
authors.forename: G
authors.initials: G
authors.lastname: Natile
authors.forename: A
authors.initials: A
authors.lastname: Barletta
authors.forename: A
authors.initials: A
authors.lastname: Paradiso
mesh_terms: D000970:Antineoplastic Agents / Q000633:toxicity*; D001692:Biological Transport; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002945:Cisplatin / Q000493:pharmacokinetics / Q000633:toxicity; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D009942:Organometallic Compounds / Q000493:pharmacokinetics / Q000633:toxicity*; D010051:Ovarian Neoplasms; D010984:Platinum / Q000493:pharmacokinetics / Q000633:toxicity; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D009942:Organometallic Compounds; C108178:dichloroplatinum(E-iminoether)2; D010984:Platinum; D002945:Cisplatin