Structure-Based Molecular Networking for the Discovery of Anti-HBV Compounds from (Decne.) C.B Clarke.

It is a crucial to find target compounds in natural product research. This study presents a concept of structure-guided isolation to find candidate active molecules from herbs. We establish a process of anti-viral sesquiterpene networking. An analysis of the networking suggested that new anti-HBV sesquiterpene may be attributable to eudesmane-, guaiane-, cadinane-, germacane- and bisabolane-type sesquiterpenes. In order to evaluate the efficiency of the structure-based molecular networking, ethanol extract of (Decne.) C.B Clarke was investigated, which led to the isolation of two guaiane-type ( and ), ten eudesmane-type (- and -), two chain ( and ) and one germacrane-type () sesquiterpenes, including seven new ones, lappaterpenes A-G (-), which are reported on herein. The absolute configurations of the new compounds were established by coupling constants, calculated ECD and ROESY correlations, as well as comparisons of optical rotation values with those of known compounds. The absolute configuration of compound was further confirmed by X-ray diffraction. Compounds - were evaluated for their potency against hepatitis B virus. Compounds , , and showed effect on HBsAg with inhibition ratios of more than 40% at 30 μM concentrations. Compounds and inhibited HBsAg secretion with the values of IC 0.73 ± 0.18 and 1.43 ± 0.54 μM, respectively. Structure-based molecular networking inspired the discovery of target compounds.