title: Activation of Platinum(IV) Prodrugs By Motexafin Gadolinium as a Redox Mediator.
abstract: Water-soluble platinum(IV) prodrugs, which proved kinetically stable to reduction in the presence of physiological concentration of ascorbate, were quickly reduced to their active form, oxaliplatin, when co-incubated with a macrocycle metallotexaphyrin (i.e., Motexafin Gadolinium (MGd)). The reduction of Pt(IV) to Pt(II) promoted by MGd occurs in cell culture as well, leading to an increase in the antiproliferative activity of the Pt(IV) species in question. The mediated effect is proportional to the concentration of MGd and gives rise to an enhancement when the prodrug is relatively hydrophilic. MGd is known to localize/accumulate preferentially in tumor tissues. Thus, the present "activation by reduction" approach may allow for the cancer-selective enhancement in the cytotoxicity of Pt(IV) prodrugs.
authors.affiliation: Department of Chemistry and Biochemistry, University of Texas at Austin, 105 E. 24th St. Stop A5300, Austin, TX, 78712-1224, USA.
authors.forename: Gregory
authors.initials: G
authors.lastname: Thiabaud
authors.affiliation: Department of Chemistry, Georgia Southern University, Statesboro, GA, 30460, USA.
authors.forename: Rebecca
authors.initials: R
authors.lastname: McCall
authors.affiliation: The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd., Unit Number: 1950, Houston, TX, 77030, USA.
authors.forename: Guangan
authors.initials: G
authors.lastname: He
authors.affiliation: Department of Chemistry, Georgia Southern University, Statesboro, GA, 30460, USA.
authors.forename: Jonathan F
authors.initials: JF
authors.lastname: Arambula
authors.affiliation: The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd., Unit Number: 1950, Houston, TX, 77030, USA. zsiddik@mdanderson.org.
authors.forename: Zahid H
authors.initials: ZH
authors.lastname: Siddik
authors.affiliation: Department of Chemistry and Biochemistry, University of Texas at Austin, 105 E. 24th St. Stop A5300, Austin, TX, 78712-1224, USA. sessler@cm.utexas.edu.
authors.forename: Jonathan L
authors.identifier: 0000-0002-9576-1325
authors.initials: JL
authors.lastname: Sessler
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D055664:Electrochemical Techniques; D006801:Humans; D008665:Metalloporphyrins / Q000737:chemistry*; D010084:Oxidation-Reduction; D010984:Platinum / Q000737:chemistry* / Q000494:pharmacology; D011355:Prodrugs / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D008665:Metalloporphyrins; D011355:Prodrugs; D010984:Platinum; C437683:motexafin gadolinium
keywords: antitumor agents; metallotexaphyrin; platinum; prodrugs; redox chemistry