Synthesis and biological evaluation of amidinourea derivatives against herpes simplex viruses

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

doi:10.3390/molecules26164927

Synthesis and biological evaluation of amidinourea derivatives against herpes simplex viruses

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

Institute of Pharmaceutical Science

Research output: Contribution to journal › Article › peer-review

7 Citations (Scopus)

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.

Original language	English
Article number	4927
Journal	Molecules
Volume	26
Issue number	16
DOIs	https://doi.org/10.3390/molecules26164927
Publication status	Published - 2 Aug 2021

Keywords

Amidines
Amidinourea
Antivirals
Guanidine
Herpes simplex virus

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10.3390/molecules26164927

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title = "Synthesis and biological evaluation of amidinourea derivatives against herpes simplex viruses",

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.",

keywords = "Amidines, Amidinourea, Antivirals, Guanidine, Herpes simplex virus",

author = "Anita Toscani and Rossana Denaro and Pacheco, {Sergio Fernando Castillo} and Matteo Biolatti and Silvia Anselmi and Valentina Dell{\textquoteright}oste and Daniele Castagnolo",

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: {\textcopyright} 2021 by the authors. Licensee MDPI, Basel, Switzerland. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.",

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AU - Toscani, Anita

AU - Denaro, Rossana

AU - Pacheco, Sergio Fernando Castillo

AU - Biolatti, Matteo

AU - Anselmi, Silvia

AU - Dell’oste, Valentina

AU - Castagnolo, Daniele

N1 - 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.

PY - 2021/8/2

Y1 - 2021/8/2

N2 - 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.

AB - 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.

KW - Amidines

KW - Amidinourea

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KW - Guanidine

KW - Herpes simplex virus

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Synthesis and biological evaluation of amidinourea derivatives against herpes simplex viruses

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