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Gold(I) complex of 1,1′-bis(diphenylphosphino) ferrocene–quinoline conjugate: a virostatic agent against HIV-1

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Abstract

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.

Graphical Abstract

In the absence of 3, TZM-bl cells were infected by a pseudovirus and this was demonstrated through luminescence in a luciferase assay. Pre-incubation of the virus with 3 decreased luminescence, indicating the anti-viral activity of 3. Complex 3 also showed cytostatic behavior with increased S-phase and G2/M phase cell cycle arrest.

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Acknowledgments

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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Author notes

  1. Debra Meyer

    Present address: Dean’s Office, Faculty of Science, University of Johannesburg, Kingsway Campus, Johannesburg, Auckland Park, 2006, South Africa

Authors and Affiliations

  1. Department of Biochemistry, University of Pretoria, Hatfield Campus, Pretoria, 0002, South Africa

    Ntombenhle Gama & Debra Meyer

  2. Inorganic Chemistry Research Group, Chemical Physics, Center for Chemistry and Chemical Engineering, Lund University, Box 124, 22100, Lund, Sweden

    Kamlesh Kumar, Erik Ekengard & Ebbe Nordlander

  3. Department of Chemistry, University of Johannesburg, Kingsway Campus, Johannesburg, Auckland Park, 2006, South Africa

    Kamlesh Kumar & James Darkwa

  4. Department of Chemistry, University of Jyväskylä, 40014, Jyväskylä, Finland

    Matti Haukka

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  1. Ntombenhle Gama
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  2. Kamlesh Kumar
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Correspondence to James Darkwa, Ebbe Nordlander or Debra Meyer.

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Gama, N., Kumar, K., Ekengard, E. et al. Gold(I) complex of 1,1′-bis(diphenylphosphino) ferrocene–quinoline conjugate: a virostatic agent against HIV-1. Biometals 29, 389–397 (2016). https://doi.org/10.1007/s10534-016-9921-9

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  • DOI: https://doi.org/10.1007/s10534-016-9921-9

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