6533b873fe1ef96bd12d5f74
RESEARCH PRODUCT
A3- and A2B-nitrocorroles: synthesis and antiviral activity evaluation against human cytomegalovirus infection
Franck GallardoLéo BucherNicolas DesboisSandrine Kappler-gratiasKerstin BystrickyKerstin BystrickyClaude P. Grossubject
PharmacologyHuman cytomegalovirus0303 health sciences010405 organic chemistrybusiness.industryOrganic ChemistryPharmaceutical Sciencemedicine.disease01 natural sciencesBiochemistryAcute toxicity0104 chemical sciences03 medical and health sciencesDrug DiscoveryToxicityCancer researchMolecular MedicineMedicineTherapeutic failurebusiness030304 developmental biologydescription
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.
year | journal | country | edition | language |
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2020-01-01 | RSC Medicinal Chemistry |