New bis(thiosemicarbazonate) gold(III) complexes inhibit HIV replication at cytostatic concentrations : potential for incorporation into virostatic cocktails

Four bis(thiosemicarbazonate)gold(III) complexes (1–4) with a general formula [Au(L)]Cl {L=L1, glyoxal-bis (N4-methylthiosemicarbazone); L2, glyoxal-bis(N4-ethylthiosemicarbazone); L3, diacetyl-bis(N4- methylthiosemicarbazone); L4, diacetyl-bis(N4-ethylthiosemicarbazone)} were synthesised and screened for activity against the human immunodeficiency virus (HIV). Complexes 1–4 were characterised using 1H-NMR and IR spectroscopy; and their purity established by micronanalysis. Complex 3 inhibited viral infection of TZM-bl cells by 98% (IC50=6.8±0.6 μM) at a non toxic concentration of 12.5 μM while complex 4 inhibited infection of these cells by 72 and 98% (IC50=5.3±0.4 μM) at concentrations of 6.25 and 12.5 μMrespectively. Themechanism of inhibition of infection in TZM-bl cells is presumably as a result of the cytostatic or anti-proliferative activity that was observed for complex 4 in real time cell electronic sensing (RT-CES) and carboxyflourescein succinimidyl ester (CFSE) analysis. Treatment of T lymphocytes from HIV infected individuals with 4 decreased CD4+ T cell expression (p=0.0049) as demonstrated by multi-parametric flow cytometry without suppressing cytokine production. None of the ligands (L1–L4) demonstrated anti-viral activity, supporting the importance of metal (gold) complexation in these potential drugs. Complexes 3 and 4were shown to have ideal lipophilicity values thatwere similarwhenshake flask (0.97±0.5 and 2.42±0.6) and in silico prediction (0.8 and 1.5) methods were compared. The activity and drug-like properties of complexes 3 and 4 suggests that these novel metal-based compounds could be combined with virus inhibitory drugs to work as cytostatic agents in the emerging class of anti-HIV drugs known as virostatics.The South African National Research Foundationhttp://www.elsevier.com/locate/jinorgbionf201

Pharmaceutical partnerships for increased access to quality essential medicines in the East Africa region

The study investigated innovation capacity of the Eastern Africa pharmaceutical manufacturing industry, identified barriers to Public/Private Partnerships (PPP) and established a framework for an impactful pharmaceutical cross-sector partnership system. Findings reveal industry’s view: that there are no adequate incentives to catalyze investing in facility upgrading and quality improvement programs, especially in the production of donor funded products such as antiretrovirals and antimalarials. Government policies, training, good manufacturing practices (GMP) compliance, manufacturing and financing/markets are important factors towards ensuring success

Phosphinogold(I) dithiocarbamate complexes : effect of the nature of phosphine ligand on anticancer properties

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Pharmaceutical partnerships for increased access to quality essential medicines in the East Africa region

The study assesses the capability/capacity of local manufacturers in the East Africa Community (EAC) region (Kenya, Tanzania, Uganda and Ethiopia) to produce essential medicines. As well, it explores how partnerships can be leveraged to expand the range of essential medicines that are manufactured in order to improve access to quality medicines through local production. The Science Granting Councils Initiative (SGCI) objective is to enhance knowledge exchange between academia and industry and stimulate private sector investments into research and innovation

HIV therapeutic possibilities of gold compounds

Highly active antiretroviral therapy (HAART) has resulted in decreased mortality and morbidity from the acquired immune deficiency syndrome caused by the human immunodeficiency virus (HIV). Drug resistance and toxicity of HAART has led to the search for novel inhibitors of HIV infection. Gold-based compounds have shown promising activity against a wide range of clinical conditions and microorganism infections including HIV-1. A typical example is auranofin which resulted in an elevated CD4? T-cell count in an HIV patient being treated for psoriatic arthritis. In addition, reports exist on gold-based inhibitors of reverse transcriptase (RT), protease (PR) and viral entry of host cells. These and other characteristics of goldbased HIV drugs are reviewed here

Phosphinogold(I) Dithiocarbamate Complexes: Effect of the Nature of Phosphine Ligand on Anticancer Properties

The reactions of potassium salts of the dithiocarbamates <b>L</b> {where <b>L</b> = pyrazolyldithiocarbamate (<b>L1</b>), 3,5-dimethylpyrazolyldithiocarbamate (<b>L2</b>), or indazolyldithiocarbamate (<b>L3</b>)} with the gold precursors [AuCl­(PPh₃)], [Au₂Cl₂­(dppe)], [Au₂Cl₂­(dppp)], or [Au₂Cl₂­(dpph)] lead to the new gold­(I) complexes [Au<b>L</b>(PPh₃)] (<b>1</b>–<b>3</b>), [Au₂<b>L</b>₂­(dppe)] (<b>4</b>–<b>6</b>), [(Au₂<b>L</b>₂)­(dppp)] (<b>7</b>–<b>9</b>), and [Au₂(<b>L</b>)_2­(dpph)] (<b>10</b>–<b>12</b>) {where dppe = 1,2-bis­(diphenylphosphino)­ethane, dppp = 1,3-bis­(diphenylphosphino)­propane, and dpph = 1,6-bis­(diphenylphosphino)­hexane}. These gold compounds were characterized by a combination of NMR and infrared spectroscopy, microanalysis, and mass spectrometry; and in selected cases by single-crystal X-ray crystallography. Compounds <b>4</b>–<b>6</b>, which have dppe ligands, are unstable in solution for prolonged periods, with <b>4</b> readily transforming to the Au₁₈ cluster [Au₁₈S₈­(dppe)₆]­Cl₂ (<b>4a</b>) in dichloromethane. Compounds <b>1</b>–<b>3</b> and <b>7</b>–<b>12</b> are all active against human cervical epithelioid carcinoma (HeLa) cells, but the most active compounds are <b>10</b> and <b>11</b>, with IC₅₀ values of 0.51 μM and 0.14 μM, respectively. Compounds <b>10</b> and <b>11</b> are more selective toward HeLa cells than they are toward normal cells, with selectivities of 25.0 and 70.5, respectively. Further tests, utilizing the 60-cell-line Developmental Therapeutics Program at the National Cancer Institute (U.S.A.), showed <b>10</b> and <b>11</b> to be active against nine other types of cancers