6533b859fe1ef96bd12b75e9

RESEARCH PRODUCT

A3- and A2B-fluorocorroles: synthesis, X-ray characterization and antiviral activity evaluation against human cytomegalovirus infection

Kerstin BystrickyKerstin BystrickyFranck GallardoLéo BucherSandrine Kappler-gratiasNicolas DesboisClaude P. GrosYoann Rousselin

subject

PharmacologyHuman cytomegalovirus0303 health sciences010405 organic chemistryChemistryStereochemistryOrganic ChemistryX-rayPharmaceutical Sciencechemistry.chemical_elementmedicine.diseaseRing (chemistry)01 natural sciencesBiochemistry0104 chemical sciencesCharacterization (materials science)03 medical and health sciencesDrug DiscoverymedicineFluorineMolecular MedicineMoleculeSelectivity030304 developmental biology

description

Twenty-nine fluorinated corroles were prepared, spectroscopically characterized, and studied for their antiviral activity against human cytomegalovirus infection. Six corroles were also fully characterized by X-ray crystallography giving insights on their geometrical features. The halogenated corroles reported herein exhibit significantly improved antiviral activity over their non-halogenated counterparts and over nitro-corrole analogs previously reported. Full activity of thirteen A3-corroles is achieved with four fluorine atoms present on the meso-phenyl ring reaching a selectivity index above 300. The maximum activity is achieved for A2B-corroles with selectivity indexes above 400. We thus demonstrate that the fluorocorrole is a highly potent platform to synthesize a new generation of anti hCMV molecules.

https://doi.org/10.1039/d0md00127a