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A3- and A2B-nitrocorroles: synthesis and antiviral activity evaluation against human cytomegalovirus infection

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Abstract

Human cytomegalovirus (hCMV) is responsible for several pathologies impacting immunocompromised patients and can trigger life-threatening infection. Several antivirals are available and are used in the clinic, but hCMV resistant strains have appeared and patients have encountered therapeutic failure. Hence, there is a constant need for new best in class or first in class antiviral molecules. We have previously shown that nitrocorroles could be used as a potent anti-hCMV agent without acute toxicity in mice. They therefore represent an excellent platform to perform structure–activity relationship (SAR) studies and to increase efficiency or reduce toxicity. We have generated original A2B- and A3-substituted nitrocorroles and have discovered optimized compounds with selectivity indices above 200. These compounds are easily synthesized in only one to two-step reactions; they are up-scalable and cost efficient. They are therefore excellent candidates for hCMV therapies and they pave the way for a new generation of molecules.

Graphical abstract: A3- and A2B-nitrocorroles: synthesis and antiviral activity evaluation against human cytomegalovirus infection

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Article information


Submitted
29 Jan 2020
Accepted
16 Apr 2020
First published
19 May 2020

RSC Med. Chem., 2020, Advance Article
Article type
Research Article

A3- and A2B-nitrocorroles: synthesis and antiviral activity evaluation against human cytomegalovirus infection

L. Bucher, S. Kappler-Gratias, N. Desbois, K. Bystricky, F. Gallardo and C. P. Gros, RSC Med. Chem., 2020, Advance Article , DOI: 10.1039/D0MD00034E

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