Design, synthesis and biological evaluation of seco-A-pentacyclic triterpenoids-3, 4-lactone as potent non-nucleoside HBV inhibitors. Issue 9 (15th May 2018) - Li, Zhijian
Graphical abstract: Highlights: 16 pentacyclic triterpene derivatives were synthesized. Pentacyclic triterpene derivatives with seco -ring-A-lactone were identified as non-nucleoside HBV inhibitors. Compounds D7 and D10 inhibited HBeAg secretion with IC50 values of 0.14 μM and 0.86 μM. Compounds B4, D7, and D10 inhibited the replication of HBV DNA effectively at the concentration of 25 μM. Compound B4 suppressed the replication of HBV cccDNA with IC50 value of 12.3 Μ (SI = 166.5). Abstract: A series of seco -A-pentacyclic triterpenoids-3, 4-lactone were synthesized and the anti-HBV activities were evaluated in vitro . Several compounds inhibited the secretion of HBV antigen and the replication of HBV DNA in micromolar level. Compounds D7 and D10, seco -A-oleanane-3, 4-lactone, suppressed the HBeAg secretion with IC50 values of 0.14 μM and 0.86 μM respectively, and the inhibitory activities were also confirmed by detecting the fluorescence intensity of FITC-labeled monoclonal mouse HBeAg antibody via flow cytometry. Compounds D7 and D10 as well as B4, ring-A cleaved 3, 30-dioic acid, also displayed remarkable inhibition on both HBV DNA replication at the concentration of 25 μM and HBV cccDNA (covalently closed circularDNA) replication with IC50 values of 33.5 μM, 32.7 μM and 12.3 μM respectively.