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Synthesis and biological evaluation of amidinourea derivatives against herpes simplex viruses

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Anita Toscani, Rossana Denaro, Sergio Fernando Castillo Pacheco, Matteo Biolatti, Silvia Anselmi, Valentina Dell’oste, Daniele Castagnolo

Original languageEnglish
Article number4927
JournalMolecules
Volume26
Issue number16
DOIs
Published2 Aug 2021

Bibliographical note

Funding Information: Acknowledgments: University of London is acknowledged for the CW Maplethorpe Fellowship to A.T. This research was supported by the Italian Ministry of Education, University and Research-MIUR (PRIN 20178ALPCM) (V.D.), “Cassa di Risparmio” Foundation of Turin (RF = 2019.2273) (V.D.), and the University of Turin (RILO 2020) (V.D. and M.B). Funding Information: Funding: This research was funded by the University of London (CW Maplethorpe Fellowship), the Italian Ministry of Education, the University and Research-MIUR (PRIN 20178ALPCM), “Cassa di Risparmio” Foundation of Turin (RF = 2019.2273) and the University of Turin (RILO 2020). Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

King's Authors

Abstract

Current therapy against herpes simplex viruses (HSV) relies on the use of a few nucleoside antivirals such as acyclovir, famciclovir and valacyclovir. However, the current drugs are ineffective against latent and drug-resistant HSV infections. A series of amidinourea compounds, designed as analogues of the antiviral drug moroxydine, has been synthesized and evaluated as potential non-nucleoside anti-HSV agents. Three compounds showed micromolar activity against HSV-1 and low cytotoxicity, turning to be promising candidates for future optimization. Preliminary mode of action studies revealed that the new compounds act in an early stage of the HSV replication cycle, just after the viral attachment and the entry phase of the infection.

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