Magnesium Complexes of Ladanein: A Beneficial Strategy for Stabilizing Polyphenolic Antivirals

Abstract

Ladanein (noted FOMe) is a potent antiviral flavone that was shown to be active on a broad spectrum of enveloped viruses. This 5,6,7-trihydroxylated flavone has, however, pharmacokinetic properties and a half-life time that need to be improved for possible therapeutic applications. We herein took advantage of the complexation properties of ladanein (Fe(III)) to evaluate its ability to bind Mg(II) (biologically relevant and redox inert ion) precursors prepared beforehand from various carboxylic acids. The 5,6,7-trihydroxylated pattern of ladanein and the ligands borne by the Mg(II) atom of the precursors were found to be essential for firm Mg(II) binding. In particular, a ternary Mg(II) complex of ladanein and pidolate (noted FOMe.MgPid) was isolated and considered for its pharmacokinetic and virucidal (Hepatitis C Virus - HCV) properties. Mg(II) complexation significantly improved the physico-chemical (solubility) and the pharmacokinetic properties (clearance, plasmatic concentration) of the flavone FOMe, while not altering its anti-HCV capacity.