Gold(I) complex of 1,1′-bis(diphenylphosphino) ferrocene–quinoline conjugate: a virostatic agent against HIV-1
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HIV infection is known for replicating in proliferating CD+ T-cells. Treatment of these cells with cytostatic (anti-proliferation) compounds such as hydroxyurea interferes with the cells’s ability support HIV replication. Combinations of such cytostatic compounds with proven anti-retroviral drugs (like ddI) are known as virostatic, and have been shown to aid in the control of the infection. The use of two different drugs in virostatic combinations however, carries the risk of adverse effects including drug–drug interactions, which could lead to augmented toxicities and reduced efficacy. Here, a novel digold(I) complex of ferrocene–quinoline (3) was investigated for cytostatic behaviour as well as anti-viral activity which if demonstrated would eliminate concerns of drug–drug interactions. The complex was synthesized and characterized by NMR, FT-IR and mass spectroscopy and the molecular structure was confirmed by X-ray crystallography. Bio-screening involved viability dyes, real time electronic sensing and whole virus assays. The complex showed significant (p = 0.0092) inhibition of virus infectivity (83 %) at 10 ug/mL. This same concentration caused cytostatic behaviour in TZM-bl cells with significant (p < 0.01) S and G2/M phase cell cycle arrest. These data supports 3 as a virostatic agent, possessing both anti-viral and cytostatic characteristics.
KeywordsHIV-1 Cytostatic Virostatic Chloroquine Gold complexes
We would like to thank the National Research Foundation (NRF) and the Technology Innovation Agency (TIA), South Africa for funding the project as well as the NRF Innovation Doctoral Scholarship for N. Gama. K. Kumar would like to thank the European Commission (Erasmus Mundus Europe Asia, EMEA) and University of Johannesburg, South Africa for a postdoctoral fellowship.
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