Tetra-chloro-(bis-(3,5-dimethylpyrazolyl)methane)gold(III) chloride: An HIV-1 reverse transcriptase and protease inhibitor

Fonteh, Pascaline Nanga; Keter, Frankline K.; Meyer, Debra; Guzei, Ilia A.; Darkwa, James

doi:10.1016/j.jinorgbio.2008.10.001

Cited by 29 publications

(18 citation statements)

References 23 publications

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“…The assay was performed according to a method previously described (Fonteh et al, 2009). Extract was tested at two concentrations 100 and 50 µg/ml.…”

Section: Hiv-1 Reverse Transcriptase Colorimetric Assaymentioning

confidence: 99%

“…In the final step, the peroxidase substrate solution [2,2'-azino-bis-(3-ethylbenzthiazoline-6-sulfonic acid)] is cleaved by the peroxidase enzyme, producing a colored reaction product. Two positive controls were used; doxorubicin, a known HIV-1 RT inhibitor (Kuete et al, 2010b;Mbaveng et al, 2011) and an in-house natural product inhibitor active against HIV-1 RT (Fonteh et al, 2009). The absorbance of the samples was read at 405 nm with a reference wavelength of 492 nm using a microtiter plate reader (Multiskan Ascent; Thermo Labsystems; USA) and was directly correlated to the level of RT activity in the sample.…”

Section: Hiv-1 Reverse Transcriptase Colorimetric Assaymentioning

confidence: 99%

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Inhibition of HIV-1 enzymes, antioxidant and anti-inflammatory activities of Plectranthus barbatus

Kapewangolo

Hussein

Meyer

2013

Journal of Ethnopharmacology

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Ethnopharmacological relevancePlectranthus barbatus is widely used in African countries as an herbal remedy to manage HIV/AIDS and related conditions. Aim of the studyTo investigate the HIV-1 inhibitory, anti-inflammatory and antioxidant properties of P. barbatus and thereby provide empirical evidence for the apparent anecdotal success of the extracts. Materials and methodsEthanolic extract of P. barbatus's leaves was screened against two HIV-1 enzymes; protease (PR) and reverse transcriptase (RT). Cytotoxicity of the extract was determined through measuring tetrazolium dye uptake of peripheral blood mononuclear cells (PBMCs) and the TZM-bl cell line. Confirmatory assays for cytotoxicity were performed using flow cytometry and real-time cell electronic sensing (RT-CES). The free radical scavenging activity of the extract was investigated with 2,2-diphenyl-1-picrylhydrazyl while the anti-inflammatory properties of the plant extract were investigated using a Th1/Th2/Th17 cytometric bead array technique. The extract exhibited strong antioxidant activity with an IC 50 of 16 µg/ml and reduced the production of pro-inflammatory cytokines indicating anti-inflammatory potential. ConclusionThis is the first demonstration of the in vitro anti HIV-1 potential of P. barbatus including direct activity as well as through the stimulation of protective immune and inflammation responses. The low cytotoxicity of the extract is also in agreement with the vast anecdotal use of this plant in treating various ailments with no reported side-effects.

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“…The assay was performed according to a method previously described (Fonteh et al, 2009). Extract was tested at two concentrations 100 and 50 µg/ml.…”

Section: Hiv-1 Reverse Transcriptase Colorimetric Assaymentioning

confidence: 99%

Section: Hiv-1 Reverse Transcriptase Colorimetric Assaymentioning

confidence: 99%

Inhibition of HIV-1 enzymes, antioxidant and anti-inflammatory activities of Plectranthus barbatus

Kapewangolo

Hussein

Meyer

2013

Journal of Ethnopharmacology

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“…Differences in compound structure might explain the different modes by which gold-based compounds inhibit either RT or PR. In Fonteh et al, a gold(III) compound is reported to inhibit both PR and RT 11 and it was observed that inhibition of PR involved both the ligand and the auric acid moiety which served as starting material for gold in the synthesis of the compound. Differences in gold(I) and gold(III) compound structure might explain why only one of the gold(I) compounds inhibits both enzymes (with only marginal anti-PR activity).…”

Section: Discussionmentioning

confidence: 99%

Novel gold(i) phosphine compounds inhibit HIV-1 enzymes

Fonteh

Meyer

2009

Metallomics

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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.

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“…Gold-based compounds have been widely exploited for anti-cancer activity (Nobili et al, 2010;Sun and Che 2009;Monim-ul-Mehboob et al, 2013) as well as for inhibition of various pathogens such as the human immunodeficiency virus (HIV) (Shapiro and Masci 1996;Fonteh et al, 2009;Fonteh et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

Impedance technology reveals correlations between cytotoxicity and lipophilicity of mono and bimetallic phosphine complexes

et al. 2015

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Label free impedance technology enables the monitoring of cell response patterns posttreatment with drugs or other chemicals. Using this technology, a correlation between the lipophilicity of metal complexes and the degree of cytotoxicity was observed. Au(L1)Cl (1), AuPd(L1)(SC 4 H 8 )Cl 3 (1a) and Au(L2)Cl (2) (L1 = (diphenylphosphino-2-pyridine); L2 = 2-(2-(diphenylphosphino)ethyl)-pyridine) were synthesised, in silico drug-likeness and structure activity relationship (SAR) monitored using impedance technology. Dose dependent changes in cytotoxicity were observed for the metal complexes resulting in IC 50s of 12.5±2.5, 18.3±8.3 and 16.9±0.5 µM for 1, 1a and 2 respectively in an endpoint assay. When a real time impedance assay was used, dose-dependent responses depicting patterns that suggested slower uptake (at a toxic 20 µM) and faster recovery of the cells (at the less toxic 10 µM) of the bimetallic complex (1a) compared to the monometallic complexes (1 and 2) was observed. These data agreed with the ADMET findings of lower aqueous solubility of 1a and non ideal lipophilicity (AlogP98 of 6.55) over more water soluble 1 and 2 with ideal lipophilicity (4.91 and 5.03 respectively) values. The additional coordination of a Pd atom to the nitrogen atom of a pyridine ring, the sulfur atom of a tetrahydrothiophene (THT) moiety and two chlorine atoms in 1a could be contributing to the observed differences when compared to the monometallic complexes. This report presents impedance technology as a means of 2 correlating drug-likeness of lipophilic phosphine complexes containing similar backbone structures and could prove valuable in filtering drug-like compounds in a drug discovery project.

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Tetra-chloro-(bis-(3,5-dimethylpyrazolyl)methane)gold(III) chloride: An HIV-1 reverse transcriptase and protease inhibitor

Cited by 29 publications

References 23 publications

Inhibition of HIV-1 enzymes, antioxidant and anti-inflammatory activities of Plectranthus barbatus

Inhibition of HIV-1 enzymes, antioxidant and anti-inflammatory activities of Plectranthus barbatus

Novel gold(i) phosphine compounds inhibit HIV-1 enzymes

Impedance technology reveals correlations between cytotoxicity and lipophilicity of mono and bimetallic phosphine complexes

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