Biocatalysed synthesis of b-O-glucosides from 9-fluorenon-2-carbohydroxyesters. Part 3: IFN-inducing and anti-HSV-2 properties

In pursuing research on the antiviral, interferon (IFN)-inducing tilorone congeners, a new series of fluoren-carboxyhydroxyesters has been prepared and biologically explored. These esters have subsequently been used as sugar acceptors in the enzymatic transglycosylation reaction using the retaining b-glycosidase from the archaeon Sulfolobus solfataricus (Ssb-Gly). Both aglycones (1-6) and corresponding b-glucosides (b-glu 1-b-glu 6) have been screened for cytotoxicity, interferon-stimulating and antiviral properties against HSV-2. It was found that the addition of compounds b-glu 5, b-glu 6 and b-glu 4 to HSV-2 infected U937 cells downregulates viral replication and triggers cells to release IFN-a/b. Taken together, the results showed improved pharmacological profiles as a consequence of glycosylation. A molecular modelling study carried out on this series of compounds completed the structural characterisation of the novel compounds.