PREPARATION, STRUCTURE AND CYTOTOXICITY OF CIS-DIAMMINEPLATINUM(II) DINUCLEAR COMPLEXES WITH 1-ALKYLURACIL AND IMIDATE LIGANDS

A series of platinum dinuclear complexes with 1-alkyluracil, cis-[Pt-2 (EtU)(2)(NH3)(4)] (NO3)(2), cis-[Pt-2(n-BuU)(2)(NH3)(4)](NO3)(2), cis- [Pt-2(BzlU)(2)(NH3)(4)] (NO3)(2) and cis-[Pt-2(NaphCH(2)U)(2)(NH3)(4)] (NO3)(2) (head-to-head, where U=uracil), and with imide ligands, cis[ Pt-2(SI)(2)(NH3)(4)] (NO3)(2) (head-to-head), cis-[Pt-2(DMGI)(2)(NH3)( 4)] (NO3)(2) (head-to-head), cis-[Pt-2(DMGI)(2)(NH3)(4)] (NO3)(2) (hea d-to-tail) and cis-[Pt-2(EMGI)(2)(NH3)(4)] (NO3)(2) (head-to-head, whe re SI = succinimidate, EMGI = 3-ethyl-3-methylglutarimidate and DMGI=3 ,3-dimethylglutarimidate) was synthesized, as well as platinum mononuc lear complexes, cis-[PtCl(SI) (NH3)(2)] and cis-[Pt(SI)(2)(NH3)(2)]. T he isomers of the dinuclear complexes (head-to-head and head-to-tail f orms) were obtained separately by fractional recystallizations. Crysta l structures of cis-[Pt-2(SI)(2)(NH3)(4)] (NO3)(2) (head-to-head),cis- [Pt-2(DMGI)(2)(NH3)(4)] (NO3)(2) (head-to-head) and cis-[Pt-2(EMGI)(2 )(NH3)(4)] (NO3)(2) (head-to-head) were determined by X-ray diffractio n analysis. Cytotoxic activity was evaluated by the IC50 value using m ouse sarcoma S-180 cells. Most head-to-head complexes are considerably active, while the corresponding head-to-tail analogues are inactive. The active complexes, in general, release ligands in saline at 37 degr ees C, and a relationship between hydrophobicity of the complexes and the IC50 value has been shown. (C) 1997 Elsevier Science S.A.