Ruiz José, Rodríguez Venancio, Cutillas Natalia, López Gregorio, Bautista Delia
Departamento de Quimica Inorganica and S.U.I.C., Edificio S.A.C.E., Universidad de Murcia, E-30071-Murcia, Spain.
Inorg Chem. 2008 Nov 3;47(21):10025-36. doi: 10.1021/ic8012359. Epub 2008 Oct 10.
The reaction of [Pt(dmba)(PPh3)Cl] [where dmba = N,C-chelating 2-(dimethylaminomethyl)phenyl] with aqueous ammonia in acetone in the presence of AgClO4 gives the acetonimine complex [Pt(dmba)(PPh3)(NH=CMe2)]ClO4 (1). The reaction of [Pt(dmba)(DMSO)Cl] with aqueous ammonia in acetone in the presence of AgClO4 gives a mixture of [Pt(dmba)(NH=CMe2)2]ClO4 (2) and [Pt(dmba)(imam)]ClO4 (3a) (where imam = 4-imino-2-methylpentan-2-amino). [Pt(dmba)(DMSO)Cl] reacts with [Ag(NH=CMe2)2]ClO4 in a 1:1 molar ratio to give [Pt(dmba)(DMSO)(NH=CMe2)]ClO4 (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)(CH2COMe)(NH=CMe2)] (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 [NBu4]2[Pt2(C6F5)4(mu-Cl)2] with [Ag(NH=CMe2)2]ClO4 in a 1:2 molar ratio produces cis-[Pt(C6F5)2(NH=CMe2)2] (6). The crystal structures of 1 x 2 Me2CO, 2, 3a, 5, and 6 have been determined. Values of IC50 were calculated for the new platinum complexes against a panel of human tumor cell lines representative of ovarian (A2780 and A2780 cisR) 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.
[Pt(dmba)(PPh₃)Cl]（其中dmba = N,C-螯合的2-(二甲基氨基甲基)苯基）在丙酮中、AgClO₄存在下与氨水反应，生成乙酮亚胺配合物[Pt(dmba)(PPh₃)(NH = CMe₂)]ClO₄ (1)。[Pt(dmba)(DMSO)Cl]在丙酮中、AgClO₄存在下与氨水反应，生成[Pt(dmba)(NH = CMe₂)₂]ClO₄ (2)和[Pt(dmba)(imam)]ClO₄ (3a)（其中imam = 4-亚氨基-2-甲基戊-2-胺）的混合物。[Pt(dmba)(DMSO)Cl]与[Ag(NH = CMe₂)₂]ClO₄以1:1摩尔比反应，生成[Pt(dmba)(DMSO)(NH = CMe₂)]ClO₄ (4)。[Pt(dmba)(DMSO)Cl]在KOH存在下、70℃于丙酮中与20%氨水反应，生成[Pt(dmba)(CH₂COMe)(NH = CMe₂)] (5)，而[Pt(dmba)(DMSO)Cl]在无KOH的情况下于丙酮中与20%氨水反应，生成[Pt(dmba)(imam)]Cl (3b)。[NBu₄]₂[Pt₂(C₆F₅)₄(μ-Cl)₂]与[Ag(NH = CMe₂)₂]ClO₄以1:2摩尔比反应，生成顺式-[Pt(C₆F₅)₂(NH = CMe₂)₂] (6)。已测定了1·2Me₂CO、2、3a、5和6的晶体结构。针对一组代表卵巢癌（A2780和A2780顺铂耐药株）和乳腺癌（T47D）的人类肿瘤细胞系，计算了新型铂配合物的IC50值。在48小时孵育时间时，配合物1、4和5对已获得顺铂耐药性的A2780细胞系显示出非常低的耐药因子。在T47D细胞系中，1、4和5比顺铂更具活性（在某些情况下高达30倍）。通过圆二色性和电泳迁移率跟踪了1、4和5的DNA加合物形成情况。
