biostudies-literatureLiu YZaozhuang UniversityNatural Science Foundation of Shandong ProvinceE5660https://www.ebi.ac.uk/biostudies/studies/S-EPMC6888404biostudies-literatureUnknown20(22)The development of Pt(IV) anticancer prodrugs to overcome the detrimental side effects of Pt(II)-based anticancer drugs is of current interest. The kinetics and reaction mechanisms of the reductive activation of the carboplatin Pt(IV) prodrug cis,trans-[Pt(cbdca)(NH3)2Cl2] (cbdca = cyclobutane-1,1-dicarboxylate) by the major small-molecule reductants in human plasma were analyzed in this work. The reductants included ascorbate (Asc), the thiol-containing molecules L-cysteine (Cys), DL-homocysteine (Hcy), and glutathione (GSH), and the dipeptide Cys-Gly. Overall second-order kinetics were established in all cases. At the physiological pH of 7.4, the observed second-order rate constants k' followed the order Asc << Cys-Gly ~ Hcy < GSH < Cys. This reactivity order together with the abundancesInternational journal of molecular sciencesInvestigations of the Kinetics and Mechanism of Reduction of a Carboplatin Pt(IV) Prodrug by the Major Small-Molecule Reductants in Human Plasma.PMC68884041020717ZR2019MB0152018BS060Xu LLiu YZhou LElding LITian HXu BShi TLiu CWang JfalseInvestigations of the Kinetics and Mechanism of Reduction of a Carboplatin Pt(IV) Prodrug by the Major Small-Molecule Reductants in Human Plasma.The development of Pt(IV) anticancer prodrugs to overcome the detrimental side effects of Pt(II)-based anticancer drugs is of current interest. The kinetics and reaction mechanisms of the reductive activation of the carboplatin Pt(IV) prodrug cis,trans-[Pt(cbdca)(NH3)2Cl2] (cbdca = cyclobutane-1,1-dicarboxylate) by the major small-molecule reductants in human plasma were analyzed in this work. The reductants included ascorbate (Asc), the thiol-containing molecules L-cysteine (Cys), DL-homocysteine (Hcy), and glutathione (GSH), and the dipeptide Cys-Gly. Overall second-order kinetics were established in all cases. At the physiological pH of 7.4, the observed second-order rate constants k' followed the order Asc << Cys-Gly ~ Hcy < GSH < Cys. This reactivity order together with the abundances2019-01-01T00:00:00Z2019 Nov2025-04-05T15:09:22.777Z2020-05-21T21:20:36ZS-EPMC68884043172672810.3390/ijms20225660