Relationships between reduction properties and cancer cell growth inhibitory activities of cis-dichloro- and cis-diiodo-Pt(IV)-ethylenediamines.

摘要: The chemical reactivities and cancer cell growth inhibitory activities of a new series cis-diiodo-Pt(IV)-ethylenediamines were compared contrasted with their cis-dichloro-Pt(IV)-counterparts cis-Diiodo-Pt(IV)-ethylenediamines bearing various axial ligands (i.e., OH, OAc, OCOCF 3 , OSO 2 CH ) prepared by oxidizing (PtI (en)] 30% H O to yield trans,cis-[PtOH I (en)], winch was then reacted gither Ac O, (CF CO) or (SO in Cl . cis-diiodo-Pt(IV) complexes readily reduced biological thiols such as L-cysteine, glutathione (GSH), bovine serum albumin (BSA) rat pH 6,9 37 °C; the kineties reduction secand-order respect thiol concentration. In contrast, cis-dichloro analogues stable presence GSH. potentials estimated means cyclovoltammetry for Pt(IV) are useful obtaining ranking order reactivity lowards thiols; however, alone cannot be used predict whether.: complex will GSH at biologically relevant concentrations. greatly facilitated platination calf thymus DNA diiodo-Pt(IV) complexes, which >90% complete after 24 h 37°C when ratio 2:1. DNA-platination trans,cis-[Pt(OH) trans,cis-[Pt(OAc) dependent on while trans,cis-[Pt(OSO showed 23% absence dichloro failed react either low (0.015 mM) high (3.0 concentrations Cell culture experiments four human lines that maximal activity iodo-Pt(IV)-ethylenediamines reached within exposure platinum complex, dichloro-Pt(IV) required much longer drug-exposure time 96 h) reach activity.