Isolation and structure-activity relationship studies of jacaranones: Anti-inflammatory quinoids from the Cuban endemic plant Jacaranda arborea (Bignoniaceae)

The Cuban endemic plant Jacaranda arborea (Bignoniaceae) has been traditionally used in folk medicine as an acaricide and for acne treatment. Two known quinoids, methyl (1-hydroxy-4-oxocyclohexa-2,5-dien-1-yl)acetate (jacaranone) (1) and its ethyl ester 2 were isolated from this species as anti-inflammatory substances. Compound 1 prominently inhibited the production of TNF-alpha in both LPS-treated macrophages and mice, with low toxicity. Structure-activity relationship studies revealed that the high electrophilicity of 1 as a Michael acceptor played an important role in these effects. Unlike in previous studies, such as those on antitumor, anti-oxidant, and anti-malarial activities, ester derivatives of 1 retained their potent anti-inflammatory activity. Our results suggest that jacaranones may target specific biomacromolecule(s) at lower concentrations than hitherto expected to exhibit potent activities. (C) 2020 Elsevier Ltd. All rights reserved.