Biocatalysed synthesis of beta-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' beta-glycosidase from the archaeon Sulfolobus solfataricus (Ssbeta-Gly). Both aglycones (1-6) and corresponding beta-glucosides (beta-glu 1-beta-glu 6) have been screened for cytotoxicity, interferon-stimulating and antiviral properties against HSV-2. It was found that the addition of compounds beta-glu 5, beta-glu 6 and beta-glu 4 to HSV-2 infected U937 cells downregulates viral replication and triggers cells to release IFN-alpha/beta. 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.
Alcaro
Stefano
S
Dipartimento di Scienze Farmacobiologiche, Università di Catanzaro Magna Graecia, Complesso Ninì Barbieri, 88021 Roccelletta di Borgia, CZ, Italy.
Arena
Adriana
A
Di Bella
Rosaria
R
Neri
Simonetta
S
Ottanà
Rosaria
R
Ortuso
Francesco
F
Pavone
Bernadette
B
Trincone
Antonio
A
Vigorita
Maria Gabriella
MG
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D002384:Catalysis; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D015536:Down-Regulation; D005449:Fluorenes / Q000737:chemistry; D005959:Glucosidases / Q000378:metabolism; D005960:Glucosides / Q000138:chemical synthesis / Q000494:pharmacology*; D006031:Glycosylation; D006561:Herpes Simplex / Q000378:metabolism / Q000473:pathology / Q000821:virology; D018258:Herpesvirus 2, Human / Q000187:drug effects*; D006801:Humans; D016898:Interferon-alpha / Q000378:metabolism*; D016899:Interferon-beta / Q000378:metabolism*; D008958:Models, Molecular; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D048229:Sulfolobus solfataricus / Q000201:enzymology; D020298:U937 Cells; D014779:Virus Replication / Q000187:drug effects*
D000970:Antineoplastic Agents; D000998:Antiviral Agents; D005449:Fluorenes; D005960:Glucosides; D016898:Interferon-alpha; D016899:Interferon-beta; C028401:9-fluorenone; D005959:Glucosidases; C104851:Sulfolobus solfataricus beta-glycosidase