title: Photoinduced reduction of Pt(IV) within an anti-proliferative Pt(IV)-texaphyrin conjugate.
abstract: In an effort to increase the stability and control the platinum reactivity of platinum-texaphyrin conjugates, two Pt(IV) conjugates were designed, synthesized, and studied for their ability to form DNA adducts. They were also tested for their anti-proliferative effects using wild-type and platinum-resistant human ovarian cancer cell lines (A2780 and 2780CP, respectively). In comparison to an analogous first-generation Pt(II) chimera, one of the new conjugates provided increased stability in aqueous environments. Using a combination of (1) H NMR spectroscopy and FAAS (flameless atomic-absorption spectrometry), it was found that the Pt(IV) center within this conjugate undergoes photoinduced reduction to Pt(II) upon exposure to glass-filtered daylight, resulting in an entity that binds DNA in a controlled manner. Under conditions in which the Pt(IV) complex is reduced to the corresponding Pt(II) species, these new conjugates demonstrated potent anti-proliferative activity in both test ovarian cancer cell lines.
authors: Department of Chemistry and Institute for Cellular and Molecular Biology, The University of Texas at Austin, 105 E. 24th Street- Stop A5300, Austin, Texas 78712-1224 (USA).
authors: Grégory
authors: G
authors: Thiabaud
authors: Jonathan F
authors: JF
authors: Arambula
authors: Zahid H
authors: ZH
authors: Siddik
authors: Jonathan L
authors: JL
authors: Sessler
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D004247:DNA / Q000378:metabolism; D015195:Drug Design; D005260:Female; D006801:Humans; D008027:Light; D009944:Organoplatinum Compounds / Q000737:chemistry* / Q000494:pharmacology; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D010053:Ovary / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D010084:Oxidation-Reduction; D011166:Porphyrins / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D011166:Porphyrins; C442892:texaphyrin; D004247:DNA
keywords: conjugates; drug design; photo-activation; platinum; texaphyrin