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Library-based discovery and characterization of Daphnane diterpenes as potent and selective HIV inhibitors in Daphne gnidium

Vidal, V. and Potterat, O. and Louvel, S. and Hamy, F. and Mojarrab, M. and Sanglier, J. J. and Klimkait, T. and Hamburger, M.. (2012) Library-based discovery and characterization of Daphnane diterpenes as potent and selective HIV inhibitors in Daphne gnidium. Journal of natural products, Vol. 75, H. 3. pp. 414-419.

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Official URL: http://edoc.unibas.ch/dok/A6043589

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Abstract

Despite the existence of an extended armamentarium of effective synthetic drugs to treat HIV, there is a continuing need for new potent and affordable drugs. Given the successful history of natural product based drug discovery, a library of close to one thousand plant and fungal extracts was screened for antiretroviral activity. A dichloromethane extract of the aerial parts of Daphne gnidium exhibited strong antiretroviral activity and absence of cytotoxicity. With the aid of HPLC-based activity profiling, the antiviral activity could be tracked to four daphnane derivatives, namely, daphnetoxin (1), gnidicin (2), gniditrin (3), and excoecariatoxin (4). Detailed anti-HIV profiling revealed that the pure compounds were active against multidrug-resistant viruses irrespective of their cellular tropism. Mode of action studies that narrowed the site of activity to viral entry events suggested a direct interference with the expression of the two main HIV co-receptors, CCR5 and CXCR4, at the cell surface by daphnetoxin (1).
Faculties and Departments:05 Faculty of Science > Departement Pharmazeutische Wissenschaften > Pharmazie > Pharmazeutische Biologie (Hamburger)
03 Faculty of Medicine > Departement Biomedizin > Division of Medical Microbiology > Molecular Virology (Klimkait)
UniBasel Contributors:Klimkait, Thomas and Potterat, Olivier and Hamburger, Matthias
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:American Society of Pharmacognosy
ISSN:0163-3864
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:08 May 2015 08:45
Deposited On:04 Jan 2013 08:35

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