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doi:10.1016/j.bmc.2005.03.016 
Copyright © 2005 Elsevier Ltd All rights reserved.
Biocatalysed synthesis of β-O-glucosides from 9-fluorenon-2-carbohydroxyesters. Part 3: IFN-inducing and anti-HSV-2 properties
Stefano Alcaroa, Adriana Arenab, Rosaria Di Bellac, Simonetta Neric, Rosaria Ottanàc, Francesco Ortusoa, Bernadette Pavoneb, Antonio Trinconed and Maria Gabriella Vigoritac, 
, 
Received 23 November 2004;
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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.
Keywords: Tilorone analogues; 9-Fluorenon-2-carbohydroxyesters; 9-Fluoren-b-O-glycosides; Enzymatic transglycosylation; IFN-inducing properties; Conformational analysis
Article Outline
- 1. Introduction
- 2. Results
- 3. Discussion
- 4. Conclusion
- 5. Experimental
- 5.1. General chemistry
- 5.2. General synthesis of hydroxyalkyl 9-oxo-2-fluorenecarboxylates (1–5)
- 5.2.1. 2-Hydroxyethyl 9-oxo-9H-2-fluorenecarboxylate (1)
- 5.2.2. 3-Hydroxypropyl 9-oxo-9H-2-fluorenecarboxylate (2)
- 5.2.3. 2-Hydroxy-2-methylethyl 9-oxo-9H-2-fluorenecarboxylate (3)
- 5.2.4. 4-Hydroxy-1-butyl 9-oxo-9H-2-fluorenecarboxylate (4)
- 5.2.5. 3-Oxa-5-hydroxy-1-penthyl 9-oxo-9H-2-fluorenecarboxylate (5)
- 5.3. Enzymatic reaction
- 5.3.1. O-β-[2-(9-Oxo-9H-2-fluorenecarbonyloxy)-1-ethyl] glucoside (β-glu 1)
- 5.3.2. O-β-[3-(9-Oxo-9H-2-fluorenecarbonyloxy)-1-propyl] glucoside (β-glu 2)
- 5.3.3. O-β-[2-Methyl-2-(9-oxo-9H-2-fluorenecarbonyloxy)-1-ethyl] glucoside (β-glu 3)
- 5.3.4. O-β-[4-(9-Oxo-9H-2-fluorenecarbonyloxy)-1-butyl] glucoside (β-glu 4)
- 5.3.5. O-β-[3-Oxa-5-(9-oxo-9H-2-fluorenecarbonyloxy)-1-pentyl] glucoside (β-glu 5)
- 5.3.6. β-9-Fluorenemethyl glucoside (β-glu 6)
- 5.4. U937 cell culture and differentiation
- 5.5. Cytotoxicity test
- 5.6. Virus
- 5.7. Interferon assay
- 5.8. Limulus test
- 5.9. Statistical evaluation
- Acknowledgements
- References
p < 0.05.