Acetonimine and 4-Imino-2-methylpentan-2-amino Platinum(II) Complexes: Synthesis and in Vitro Antitumor Activity

作者：Ruiz Jose^*; Rodriguez Venancio; Cutillas Natalia; Lopez Gregorio; Bautista Delia

来源：Inorganic Chemistry, 2008, 47(21): 10025-10036.

DOI：10.1021/ic8012359

The reaction of [Pt(dmba)(PPh(3))Cl] [where dmba = N,C-chelating 2-(dimethylaminomethyl)phenyl] with aqueous ammonia in acetone in the presence of AgClO(4) gives the acetonimine complex [Pt(dmba)(PPh3)(NH=CMe(2))]ClO(4) (1). The reaction of [Pt(dmba)(DMSO)Cl] with aqueous ammonia in acetone in the presence of AgClO(4) gives a mixture of (Pt(dmba)(NH=CMe(2))(2)]ClO(4) (2) and [Pt(dmba)(imam)]ClO(4) (3a) (where imam = 4-imino-2-methylpentan-2-amino). [Pt(dmba)(DMSO)Cl] reacts with [Ag(NH=CMe(2))(2)]ClO(4) in a 1:1 molar ratio to give [Pt(dmba)(DMSO)(NH=CMe(2))]ClO(4) (4). The reaction of [Pt(dmba)(DMSO)Cl] with 20% aqueous ammonia in acetone at 70 degrees C in the presence of KOH gives [Pt(dmba)(CH(2)COMe)(NH=CMe(2))] (5), whereas the reaction of [Pt(dmba)(DMSO)Cl] with 20% aqueous ammonia in acetone in the absence of KOH gives [Pt(dmba)(imam)]Cl (3b). The reaction of (NBu(4)](2)[Pt(2)(C(6)F(5))(4)(mu-Cl)(2)] with [Ag(NH=CMe(2))(2)]ClO(4) in a 1:2 molar ratio produces cis-[Pt(C(6)F(5))(2)(NH=CMe(2))(2)] (6). The crystal structures of 1 . 2Me(2)CO, 2, 3a, 5, and 6 have been determined. Values of IC(50) were calculated for the new platinum complexes against a panel of human tumor cell lines representative of ovarian (A2780 and A2780cisR) and breast cancers (T47D). At 48 h incubation time complexes 1, 4, and 5 show very low resistance factors against an A2780 cell line which has acquired resistance to cisplatin. 1, 4, and 5 were more active than cisplatin in T47D (up to 30-fold in some cases). The DNA adduct formation of 1, 4, and 5 was followed by circular dichroism and electrophoretic mobility.

• 出版日期2008-11-3