title: Correlation of the in vitro cytotoxic and in vivo antitumor activities of gold(I) coordination complexes.
abstract: A series of gold(I) coordination complexes including analogues of the antiarthritic agent auranofin 1 were evaluated for in vitro cytotoxic potency against both B16 melanoma cells and P388 leukemia cells and in vivo antitumor activity against P388 leukemia in mice. A number of the complexes showed potent cytotoxic activity in vitro and antitumor activity in vivo, with the phosphine-coordinated gold(I) thiosugar complexes demonstrating the greatest in vitro and in vivo activity. The data compiled for 63 complexes of the general structural formula LAuX provide the basis for the following observations: potent in vitro cytotoxic activity is observed for substituted (phosphine) gold complexes, lack of potency in vitro correlates well with lack of antitumor activity, potent cytotoxicity in vitro is not necessarily predictive of activity in vivo, in vivo antitumor activity is generally optimized by ligation of Au(I) with a substituted phosphine and a thiosugar.
authors.forename: C K
authors.initials: CK
authors.lastname: Mirabelli
authors.forename: R K
authors.initials: RK
authors.lastname: Johnson
authors.forename: D T
authors.initials: DT
authors.lastname: Hill
authors.forename: L F
authors.initials: LF
authors.lastname: Faucette
authors.forename: G R
authors.initials: GR
authors.lastname: Girard
authors.forename: G Y
authors.initials: GY
authors.lastname: Kuo
authors.forename: C M
authors.initials: CM
authors.lastname: Sung
authors.forename: S T
authors.initials: ST
authors.lastname: Crooke
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001310:Auranofin; D006051:Aurothioglucose / Q000031:analogs & derivatives / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D006046:Gold / Q000494:pharmacology*; D007941:Leukemia P388 / Q000188:drug therapy; D008545:Melanoma / Q000473:pathology; D051379:Mice; D012995:Solubility; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D006051:Aurothioglucose; D001310:Auranofin; D006046:Gold