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

Abstract

HIV infection is known for replication 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 ferrocenequinoline (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.