title: Tetra-chloro-(bis-(3,5-dimethylpyrazolyl)methane)gold(III) chloride: An HIV-1 reverse transcriptase and protease inhibitor.
abstract: The title compound ([3,5-Me(2)bpzaH(2)][AuCl(4)]Cl, 1) (Me(2)bpza=bis(3,5-dimethylpyrazolyl)acetic acid), was prepared by reacting H[AuCl(4)] with 3,5-Me(2)bpza; and spectroscopically and structurally characterized. In the solid state structure of 1, the pyrazolyl ligand is doubly protonated to form two strong charge assisted hydrogen bonds of the type N(+)Hcdots, three dots, centeredCl(-) with the single chloride anion whilst the [AuCl(4)](-) anion remains discrete. The anti-HIV-1 activity of 1 was determined by a colorimetric direct enzyme reverse transcriptase (RT) assay and a fluorogenic protease (PR) assay. Compound 1 significantly (p<0.05) inhibited RT over a concentration range of 5-250muM and inhibited HIV-1 protease at 100muM. Compound 1 inhibited two very important HIV-1 enzymes (RT and PR) in direct enzyme assays and therefore warrants further evaluation.
authors.affiliation: Department of Biochemistry, University of Johannesburg, Auckland Park, Kingsway Campus, Johannesburg 2006, South Africa.
authors.forename: Pascaline N
authors.initials: PN
authors.lastname: Fonteh
authors.forename: Frankline K
authors.initials: FK
authors.lastname: Keter
authors.forename: Debra
authors.initials: D
authors.lastname: Meyer
authors.forename: Ilia A
authors.initials: IA
authors.lastname: Guzei
authors.forename: James
authors.initials: J
authors.lastname: Darkwa
mesh_terms: D002478:Cells, Cultured; D018360:Crystallography, X-Ray; D016333:HIV Protease / Q000187:drug effects*; D017320:HIV Protease Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors*; D015497:HIV-1 / Q000187:drug effects* / Q000201:enzymology; D006801:Humans; D015394:Molecular Structure; D050607:Organogold Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D018894:Reverse Transcriptase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D017320:HIV Protease Inhibitors; D050607:Organogold Compounds; D018894:Reverse Transcriptase Inhibitors; C538910:tetrachloro(bis(3,5-dimethylpyrazolyl)methane)gold(III); C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase; D016333:HIV Protease