Anthelmintic activity of selected neolignans and semisynthetic derivatives from Styrax suberifolius

The plant metabolite, equiselignan B (2), isolated from the fruits of Styrax suberifolius was used to generate a semisynthetic library. Extraction and purification studies yielded large quantities (similar to 70 mg) of 2, a new glycoside, suberifolioside A (1), and the previously described neolignan egonol (3). The planer structure of 1 was established following 1D/2D NMR and MS analyses, and its absolute configuration was determined by X-ray diffraction studies. Acid hydrolysis of 1 yielded an additional amount of scaffold 2 (436 mg) that was subsequently converted into seven new ether derivatives (4-10) and two new ester derivatives (11-12) using commercially available alkyl halides and acyl chlorides, respectively. The chemical structures of the new semisynthetic ether and ester derivatives were assigned by spectroscopic and spectrometric analyses. Subsequently, compounds 1-12 were evaluated for their anthelmintic activity on exsheathed third-stage larvae (xL3s) and fourth-stage larvae (L4s) of Haemonchus contortus (barber's pole worm) - a highly pathogenic parasitic roundworm of ruminant livestock. Ether derivative 5 displayed significant anthelmintic activity against both xL3s and L4s, resulting in a 66-73 % reduction in motility at 50 mu M after 168 h (xL3s) or 90 h (L4s) of exposure and IC50 values of 24-30 mu M. This derivative also induced curved (Cur), evisceration (Evi) and skinny (Ski) phenotypes in affected larvae. Compounds 1, 9 and 12 also had marked activity against L4s, which indicate that the neolignan structure class warrants further investigation for anthelmintic activity.