title: Biological properties of two gold(III) complexes: AuCl3(Hpm) and AuCl2(pm).
abstract: The reactivity in solution of two recently characterized gold(III) complexes, AuCl3(Hpm) and AuCl2(pm), has been investigated in view of their potential use as anti-cancer agents. In water, both compounds undergo relatively fast hydrolysis of the bound chlorides without loss of the heterocycle ligand; the process is much faster within a physiological buffer. When the two gold(III) complexes react with proteins like albumin or transferrin, reduction of gold(III) to gold(I) and/or hydrolysis is observed. On the other hand, both complexes bind rapidly and tightly to either polynucleotides or calf thymus DNA, with gold remaining in the +3 oxidation state. Circular dichroism investigations reveal a large perturbation of DNA conformation upon gold(III) binding; preferential binding to GC sequences is shown. Cytotoxicity studies on a number of tumor cell lines demonstrate a good activity of these gold(III) complexes compared to cisplatin. However, quick hydrolysis and/or reduction of these compounds under physiological conditions may represent a severe limitation to their use.
authors.affiliation: Department of Chemistry, University of Florence, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Calamai
authors.forename: S
authors.initials: S
authors.lastname: Carotti
authors.forename: A
authors.initials: A
authors.lastname: Guerri
authors.forename: L
authors.initials: L
authors.lastname: Messori
authors.forename: E
authors.initials: E
authors.lastname: Mini
authors.forename: P
authors.initials: P
authors.lastname: Orioli
authors.forename: G P
authors.initials: GP
authors.lastname: Speroni
mesh_terms: D000970:Antineoplastic Agents / Q000633:toxicity*; D002470:Cell Survival / Q000187:drug effects; D002712:Chlorides / Q000633:toxicity; D002945:Cisplatin / Q000633:toxicity; D004247:DNA / Q000737:chemistry* / Q000187:drug effects; D017612:Gold Compounds / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D006801:Humans; D009690:Nucleic Acid Conformation / Q000187:drug effects; D011089:Polydeoxyribonucleotides / Q000737:chemistry* / Q000378:metabolism; D012709:Serum Albumin / Q000737:chemistry* / Q000378:metabolism; D012996:Solutions; D013053:Spectrophotometry; D014168:Transferrin / Q000737:chemistry* / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D002712:Chlorides; D017612:Gold Compounds; D011089:Polydeoxyribonucleotides; D012709:Serum Albumin; D012996:Solutions; D014168:Transferrin; C038016:gold chloride; C024568:gold tetrachloride, acid; D004247:DNA; D002945:Cisplatin