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ID: ALA2086391

Journal: Bioorg Med Chem Lett

Title: Structure based molecular design, synthesis and biological evaluation of α-pyrone analogs as anti-HSV agent.

Authors: Karampuri S, Bag P, Yasmin S, Chouhan DK, Bal C, Mitra D, Chattopadhyay D, Sharon A.

Abstract: Several options for treating Herpes Simplex Virus type 1 and type 2 are available. However, non-specific inhibition and drug resistance warrants the discovery of new anti-herpetic compounds with better therapeutic profile or different mode of action. The non-nucleoside inhibitors of HSV DNA polymerase target the site that is less important for the binding of a natural nucleoside or nucleoside inhibitors. In the present study, we have explored the possibility to find a new lead molecule based on α-pyrone analogs as non-nucleoside inhibitors using structure based modeling approach. The designed molecules were synthesized and evaluated for anti-HSV activity using MTT assay. The compound 5h with EC(50) 7.4μg/ml and CC(50) 52.5μg/ml was moderately active against HSV when compared to acyclovir. A plaque reduction assay was also carried out and results reveal that 5h is more effective against HSV-1 with better selective index of 12.8 than against HSV-2 (SI=3.6). The synthesized compounds were also evaluated for anti-HIV activity, but none were active.

CiteXplore: 22921079

DOI: 10.1016/j.bmcl.2012.07.098