Synthesis and Anti-HBV Activity Evaluation of Matijin-Su Derivatives Containing Trifluoromethyl
CUI Jing1,2,3, LU Wei2,3,QIU Jing-ying4,ZENG Xiao-ping2,3,LIANG Guang-yi2,3*, XU Bi-xue2,3*
1. College of Pharmacy, Guizhou University, Guiyang 550025, China; 2. State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang 550014, China; 3. The Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academy of Sciences, Guizhou Provincial Engineering Research Center for Noctural Drugs, Guiyang 550014, China; 4. Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou 221004, China
Abstract：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.
SHEPARD C W, SIMARD E P, FINELLI L, et al. Hepatitis B virus infection:epidemiology and vaccination[J].Epidemiol Rev, 2006, 28(1):112-125.
[2]
ASSELAH T, RIPAULT M P, MARCELLIN P, et al. The current status of antiviral therapy of chronic hepatitis B[J].J Clin Virol,2005,34(1):115-124.
[3]
GLEBE D. Recent advances in hepatitis B virus research:a German point of view[J]. World J Gastroenterol,2007, 13(1):8-13.
[4]
LIAW Y F, SUNG J J,CHOW W G, et al. Lamivudine for patients with chronic hepatitis B and advanced liver disease[J]. N Engl J Med, 2004, 351(15):1521-1531.
[5]
TILLMANN H L. Antiviral therapy and resistance with hepatitis B virus infection[J]. World J Gastroenterol,2007, 13(1):125-140.
[6]
YUEN M F, SETO W K, CHOW D H, et al. Long-term lamivudine therapy reduces the risk of long-term complications of chronic hepatitis B infection even in patients without advanced disease[J]. Antiv Ther, 2007,12(8):1295-1303.
[7]
PARK N H, SONG I H, CHUNG Y H. Chronic hepatitis B in hepatocarcinogenesis[J]. Postgrad Med J,2006,82(970):507-515.
[8]
XU B X, HUANG Z M, LIU C X, et al. Synthesis and anti-hepatitis B virus activities of Matijing-Su derivatives[J]. Bioorg Med Chem, 2009,17(8):3118-3125.
[9]
QIU J Y, XU B X, LIANG G Y, et al. Synthesis and biological evaluation of Matijing-Su derivatives as potent anti-HBV agents[J]. Bioorg Med Chem, 2011,19(18):5352-5360.
[10]
YUAN J, LIU Q C, XU G C, et al. Synthesis and anti-hepatitis B virus activities of Matijin-Su derivatives with potential for hepatic targeting[J]. Chin J Org Chem(有机化学), 2015, 35(10):2176-2183.
[11]
MÜLLER K, FAEH C, DIEDERICH F. Fluorine in pharmaceuticals:looking beyond intuition[J].Science,2007,317(5846):1881-1886.
[12]
KUKHAR V P,SOROCHINSKY A E,SOLOSHONOK V A. Practical synthesis of fluorine-containing α- and β-amino acids:recipes from Kiev,Ukraine[J]. Future Med Chem,2009,1(5):793-819.
[13]
HU L, CHEN X M, TONG Y, et al. Synthesis and anti-tumor activities of L-phenylalanine dipeptide derivatives[J]. Chin Pharm J(中国药学杂志),2016,51(21):1831-1838.
[14]
XU G C, LIU Q C, YUAN J, et al. Synthesis and anti-hepatitis B virus activities of galactopyranosyl derivatives of Matijin-Su [J]. Chin J Org Chem(有机化学),2016,36(7):1617-1625.
2019, Vol. 54 
