title: Synthesis and activity of [{Cis-PtCl(NH3)2}2µ{trans-Pt(3-Hydroxypyridine)2(H2N(CH2)6NH2)2}]Cl4 in the human ovarian tumour models.
abstract: A novel trinuclear platinum compound with a cis-geometry for terminal metal centres coded as QH1 has been synthesized, characterized and investigated for activity against the human ovarian A2780, A2780cisR and A2780ZD0473R cancer cell lines. The cellular accumulation of platinum, level of platinum-DNA binding and the nature of interaction of the compound with pBR322 plasmid DNA have also been determined. QH1 is found to be more active against the resistant cell lines than the parent cell line, thus indicating that the compound has been able to overcome mechanisms of resistance operating in the A2780cisR and A2780ZD0473R cell lines. The high activity of QH1 is associated with high platinum accumulation and high level of platinum-DNA binding in all the three ovarian cancer cell lines. Provided QH1 has the right toxicity profile and its in vitro activity is matched with sufficient activity in vivo, the compound has the potential for development as a novel platinum-based anticancer drug targeted to the ovarian cancer.
authors.affiliation: Discipline of Biomedical Science, School of Medical Sciences, The University of Sydney, Cumberland Campus C42, 75 East Street, Lidcombe, NSW 1825, Australia.
authors.forename: Shahnaz A H
authors.initials: SA
authors.lastname: Hamad
authors.forename: Philip
authors.initials: P
authors.lastname: Beale
authors.forename: Jun Qing
authors.initials: JQ
authors.lastname: Yu
authors.forename: Keith
authors.initials: K
authors.lastname: Fisher
authors.forename: Fazlul
authors.initials: F
authors.lastname: Huq
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D015394:Molecular Structure; D009944:Organoplatinum Compounds / Q000138:chemical synthesis* / Q000494:pharmacology*; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds