title: Tuning the metabolism of the anticancer drug cisplatin with chemoprotective agents to improve its safety and efficacy.
abstract: Numerous in vivo studies have shown that the severe toxic side-effects of intravenously administered cisplatin can be significantly reduced by the co-administration of sulfur-containing 'chemoprotective agents'. Using a metallomics approach, a likely biochemical basis for these potentially useful observations was only recently uncovered and appears to involve the reaction of chemoprotective agents with cisplatin-derived Pt-species in human plasma to form novel platinum-sulfur complexes (PSC's). We here reveal aspects of the structure of two PSC's and establish the identification of an optimal chemoprotective agent to ameliorate the toxic side-effects of cisplatin, while leaving its antineoplastic activity largely intact, as a feasible research strategy to transform cisplatin into a safer and more effective anticancer drug.
authors.affiliation: Department of Chemistry, University of Calgary, 2500 University Drive NW, Calgary, AB T2N 1N4, Canada. jgailer@ucalgary.ca.
authors.forename: Melani
authors.initials: M
authors.lastname: Sooriyaarachchi
authors.affiliation: Molecular and Environmental Science Research Group, Department of Geological Sciences, University of Saskatchewan, Saskatoon, S7N 5E2, Canada and Toxicology Centre, University of Saskatchewan, Saskatoon, SK S7N 5B3, Canada and Department of Chemistry, University of Saskatchewan, Saskatoon, SK S7N 5C9, Canada.
authors.forename: Graham N
authors.initials: GN
authors.lastname: George
authors.affiliation: Molecular and Environmental Science Research Group, Department of Geological Sciences, University of Saskatchewan, Saskatoon, S7N 5E2, Canada and Toxicology Centre, University of Saskatchewan, Saskatoon, SK S7N 5B3, Canada and Department of Chemistry, University of Saskatchewan, Saskatoon, SK S7N 5C9, Canada.
authors.forename: Ingrid J
authors.initials: IJ
authors.lastname: Pickering
authors.affiliation: Division of Pediatric Oncology, Alberta Children's Hospital, Calgary, AB T3B 6A8, Canada.
authors.forename: Aru
authors.initials: A
authors.lastname: Narendran
authors.affiliation: Department of Chemistry, University of Calgary, 2500 University Drive NW, Calgary, AB T2N 1N4, Canada. jgailer@ucalgary.ca.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Gailer
mesh_terms: D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000737:chemistry / Q000378:metabolism*; D002945:Cisplatin / Q000009:adverse effects* / Q000737:chemistry / Q000378:metabolism*; D015195:Drug Design; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy; D017671:Platinum Compounds / Q000737:chemistry*; D020011:Protective Agents / Q000737:chemistry*; D013457:Sulfur Compounds / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D017671:Platinum Compounds; D020011:Protective Agents; D013457:Sulfur Compounds; D002945:Cisplatin