三氟甲基取代马蹄金素衍生物的合成及其抗乙肝病毒活性研究

OBJECTIVE: To design and synthesize derivatives of Matijin-Su (MTS) containing trifluoromethyl group and investigate their anti-HBV activities in vitro. METHODS: Taking MTS as lead compound, target compounds were prepared by acylation, alkylation and hydrolysis, etc. The cytotoxicities and anti-HBV activities of the target compounds were tested with MTT method.RESULTS Twenty derivatives of MTS containing trifluoromethyl were synthesized and their structures were confirmed by ¹H-NMR, ¹³C-NMR and MS(ESI). The anti-HBV activities of those compounds were evaluated in HepG2 2.2.15 cells. The screening RESULTS: showed that compounds 3b, 6a, 6c, 6d, 6h-6j and 6n had HBV inhibitory effect for HepG2 2.2.15 cells. Compounds 3b, 6d and 6n exhibited significant anti-HBV activity with IC₅₀ values of 11.74, 8.73 and 11.41 μmol•L^-1. CONCLUSION: Incorporation of trifluoromethyl into MTS derivatives can lead to profound changes in their anti-HBV activity, and could be worth of further research.