Inhibitory Effects of Novel 3-Hydroxy-4-Pyridinones with Iron Chelating Activity against Production of HIV Virions

Background and purpose: The need to find new antiviral compounds is increasing due to the emergence of resistant strains and toxicity of currently available HIV drugs. In this research the inhibitory activity of a number of novel iron chelating compounds derived from 3-Hydroxy-4-pyridinosnes was studied. Materials and methods: Single cycle replicable (SCR) virion was produced by transfection of HEK293T cells with pmzNL4-3, pSPAX2 and pMD2G plasmids. HEK cells were infected with SCR virus and the production of new virions was evaluated by p24 ELISA. Also, cytotoxicity of these compounds was investigated by XTT method and then the effect of compounds on viral infection was examined by GFP-expressing virions. Results: PhH, PhHB, DNB, TsB, AbphE and Adlb compounds had the ability of inhibition of virus production insofar as PhH, PhHB, DNB, TsB, AbphE and Adlb inhibited the viral production with IC50 of 63, 43, 10, 73, 12 and78µ M, respectively. DNB and AbphE showed high toxicity for target cells (CC50 of 113 and 112µM). Similar activity was found in single round infection assay compared to the results of replication study. Conclusion: This study found derivatives of 3-Hydroxy-4-pyridinosnes effective in preventing the HIV virus. Compounds with high anti-viral potential and low cytotoxicity are promising candidate for more anti-viral studies.