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

Abstract: 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’ β-glycosidase from the archaeon Sulfolobus solfataricus (Ssβ-Gly). Both aglycones (1–6) and corresponding β-glucosides (β-glu 1–β-glu 6) have been screened for cytotoxicity, interferon-stimulating and antiviral properties against HSV-2. It was found that the addition of compounds β-glu 5, β-glu 6 and β-glu 4 to HSV-2 infected U937 cells downregulates viral replication and triggers cells to release IFN-α/β. 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. [Copyright &y& Elsevier]