目的设计合成含三氟甲基取代的马蹄金素(Matijin-Su,MTS)衍生物,并对其体外抗乙肝病毒活性进行研究。方法以MTS为先导化合物,经酰化、烷基化及水解等反应合成目标化合物,通过四甲基偶氮唑蓝(MTT)法评价化合物的细胞毒性和抗乙肝病毒活性。结果共合成20个含三氟甲基取代的MTS衍生物,其结构经1H-NMR、13C-NMR和MS(ESI)表征,对所合成的目标化合物以Hep G2 2. 2. 15细胞进行体外抗HBV活性测试,活性测试结果显示,3b、6a、6c、6d、6h~6j和6n对Hep G2 2. 2. 15细胞均有一定的抑制作用,其中3b、6d及6n显示较强的抗HBV活性,其IC50达到了11. 74、8. 73和11. 41μmol·L^-1。结论 B环的间位进行三氟甲基取代的MTS衍生物可普遍提高抗HBV活性,具有进一步研究的价值。
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 Hep G2 2. 2. 15 cells. The screening results showed that compounds 3b,6a,6c,6d,6h-6j and 6n had HBV inhibitory effect for Hep G2 2. 2. 15 cells. Compounds 3b,6d and 6n exhibited significant antiHBV 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.
Chinese Pharmaceutical Journal
anti-hepatitis B virus activity