Anti-herpes simplex virus activity of alkaloids isolated from Stephania cepharantha

By screening water and MeOH extracts of 30 Chinese medicinal plants for the ir anti-herpes simplex virus (HSV)-1 activity, a MeOH extract of the root t ubers of Stephania cepharantha HAYATA showed the most potent activity on th e plaque reduction assay with an IC50 value of 18.0 mu g/ml. Of 49 alkaloid s isolated from the MeOH extract, 17 alkaloids were found to be active agai nst HSV-1, including 13 bisbenzylisoquinoline, 1 protoberberine, 2 morphina ne and 1 proaporphine alkaloids, while benzylisoquinoline and hasubanane al kaloids were inactive. Although S-methylcrotsparine was active against HSV- 1, as well as HSV-1 thymidine kinase deficient (acyclovir resistant type, H SV-1 TK-) and HSV-2 (IC50 values of 8.3, 7.7 and 6.7 mu g/ml, respectively) , it was cytotoxic. FK-3000 was found to be the most active against HSV-1, HSV-1 TK- and HSV-2 (IC50 values of 7.8, 9.9 and 8.7 mu g/ml) with in vitro therapeutic indices of 90, 71 and 81. respectively. FK-3000 was found to b e a promising candidate as an anti-HSV agent against HSV-1, acyclovir (ACV) resistant-type HSV-1 and HSV-2.