title: Novel gold(I) phosphine compounds inhibit HIV-1 enzymes.
abstract: The increasing incidence of human immunodeficiency virus (HIV) infection and the associated acquired immune deficiency syndrome (AIDS) mortality rates as well as the sometimes severe side effects of highly active anti retroviral therapy (HAART) warrants the continuous search for new, less toxic drug candidates. The anti-HIV activity (inhibition of reverse transcriptase-RT and protease-PR in direct enzyme assays) of eleven gold(i) phosphine compounds are reported here. Uptake of the compounds by peripheral blood mononuclear cells (PBMCs) was demonstrated by inductively coupled plasma atomic emission spectroscopy (ICP-AES) while the effect of the compounds on cell viability was assessed using flow cytometry with annexin V and propidium iodide (PI). Of the 11 gold compounds tested, 7 significantly (p < 0.05) inhibited RT activity at concentrations of 25 and 250 μM while 3 compounds significantly inhibited its activity at 6.25 μM. In the anti-protease assay, 4 of the compounds significantly inhibited the enzyme (p < 0.05) at 100 μM. All of the compounds were taken up by PBMCs (demonstrated by ICP-AES) and were non toxic to these cells at clinically tolerable concentrations. The potential of these novel gold(i) phosphine compounds as anti-HIV agents is therefore promising and worthy of further investigation.
authors.affiliation: Biochemistry Department, University of Johannesburg, Auckland Park Kingsway Campus, P.O. Box 524 Auckland Park, 2006, Johannesburg, South Africa.
authors.forename: Pascaline
authors.initials: P
authors.lastname: Fonteh
authors.forename: Debra
authors.initials: D
authors.lastname: Meyer
mesh_terms: D002470:Cell Survival / Q000187:drug effects; D005434:Flow Cytometry; D017612:Gold Compounds / Q000097:blood / Q000494:pharmacology*; D016333:HIV Protease / Q000378:metabolism; D017320:HIV Protease Inhibitors / Q000097:blood / Q000494:pharmacology*; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors*; D015497:HIV-1 / Q000201:enzymology*; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D010720:Phosphines / Q000097:blood / Q000494:pharmacology*; D018894:Reverse Transcriptase Inhibitors / Q000097:blood / Q000494:pharmacology*; D013054:Spectrophotometry, Atomic
chemical_list: D017612:Gold Compounds; D017320:HIV Protease Inhibitors; D010720:Phosphines; D018894:Reverse Transcriptase Inhibitors; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase; D016333:HIV Protease