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Discovery and mechanism of action of Novel Baicalein modified derivatives as potent antihepatitis agent.
Virology 2017 July
Anti-hepatitis B virus (HBV) activity was evaluated in HepG2 2.2.15 cells by novel Baicalein derivatives. The result showed that compounds 4k and 4h was found to be effective anti-HBV agent. Further, the effect of compounds 4k and 4h showed dose-dependent inhibition of HBV-DNA as compared to control together with significant inhibition of HbeAG and HbsAG expression in the tested dose. Both compounds showed considerable affinity against the HepG2.2.15 cells. Moreover, the docking study of compound 4k was carried out with HLA molecule showing excellent intermolecular interactions with the receptor via creation of numerous bonds with Ser5, Thr27, Asp29 and Phe8. The compound 4k showed significant effect on the HO-1 expression in HepG2.2.15 cells together with excellent anti-HBV activity in transgenic mouse confirmed by biochemical and histopathological parameters. Compound 4k also showed excellent pharmacokinetic profile in experimental animal and thus, provide a novel class of potent anti-HBV agents.
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