Synthesis and anti-leishmanial activities of uniflorol analogues

Abstract

Chromanones are a subset of the benzopyran family, and display diverse biological activities, both as natural products and synthetic derivatives. Among these, we selected the natural product uniflorol, a 4-chromanone with an α,β-unsaturated ketone side chain, as a lead compound due to its reported anti-leishmanial properties. We designed and synthesised four series of novel compounds, varying the substitution patterns around the benzopyran core, and evaluated the compounds for anti-leishmanial activity against amastigotes of L. infantum. We prepared and characterised 24 novel compounds; upon screening, 12 compounds demonstrated activity values of <50 μM, with the most potent compound, 16d, having an IC₅₀ of 7.29 μM. Activity was favoured in compounds bearing a phenylalkenyl motif, such as cinnamyl, styryl or a more lipophilic extension, and amide analogues retained activity. Uniflorol analogues display promise as novel architectures towards the development of potential anti-leishmanial agents.