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 o 0.05) inhibited RT activity at concentrations of 25 and 250 mM while 3 compounds significantly inhibited its activity at 6.25 mM. In the anti-protease assay, 4 of the compounds significantly inhibited the enzyme (p o 0.05) at 100 mM. 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.

Novel bio-friendly and non-toxic thiocarbohydrate stabilizers of gold nanoparticles

“…These two drugs were chosen due to their activities towards HIV 82 and cancer cells 83,84 respectively, since our main aim is to develop non-toxic stabilizers as delivery vehicles for anticancer and HIV drugs. These two drugs were chosen due to their activities towards HIV 82 and cancer cells 83,84 respectively, since our main aim is to develop non-toxic stabilizers as delivery vehicles for anticancer and HIV drugs.…”

{μ-1,2-Bis[bis(4-methoxyphenyl)phosphanyl]-1,2-diethylhydrazine-κ2P:P′}bis[chloridogold(I)] tetrahydrofuran disolvate

“…The Au-Au distance within the complex is 3.141 (2) Å, well within the range of aurophilic interactions (described in Holleman & Wiberg, 2001, as being normally between 2.7 Å and 3.4 Å). Other bond lengths are within The biological activity of the title complex is discussed in Fonteh & Meyer (2009), and related structures with other dialkyl hydrazine derivatives have been also reported (Kriel et al, 2011a,b,c;Reddy et al, 1994Reddy et al, , 1995Slawin et al, 2002).…”

“…For AuÁ Á ÁAu interactions, see: Holleman & Wiberg (2001). For the biological activity of the title complex, see: Fonteh & Meyer (2009). Table 1 Hydrogen-bond geometry (Å , ).…”

Hyphenated techniques as tools for speciation analysis of metal-based pharmaceuticals: developments and applications

“…A further promising new area of application for goldbased drugs was recently reported by Fonteh et al and Lewis et al, who obtained initial promising results when gold(I) phosphine compounds were applied against HIV [106][107][108]. The potential of gold as a novel therapeutic approach for autism was recently highlighted [109].…”