Biological Properties and Absolute Configuration of Flavanones From Calceolariathyrsiflora Graham

Abstract

Flavanones (-)-(2<i>S</i>)-5,4'-dihydroxy-7-methoxyflavanone (1) and (-)-(2<i>S</i>)-5,3',4'-trihydroxy-7-methoxyflavanone (2) were isolated from the extracts of <i>Calceolaria</i> <i>thyrsiflora</i> Graham, an endemic perennial small shrub growing in the central zone of Chile. The absolute configuration of these compounds was resolved by optical rotation experiments and <i>in silico</i> calculations. Three analogs (3, 4, and 5) were synthesized to do structure-activity relationships with the biological assays studied. Biological tests revealed that only flavanone 2 exhibited a moderate inhibitory activity against the methicillin-resistant strain <i>S</i>. <i>aureus</i> MRSA 97-77 (MIC value of 50 µg/ml). In addition, flavanone 2 showed a potent, selective, and competitive inhibition of 5-hLOX, which supports the traditional use of this plant as an anti-inflammatory in diseases of the respiratory tract. Also, 2 exhibited cytotoxic and selective effects against B16-F10 (8.07 ± 1.61 µM) but 4.6- and 17-fold lesser activity than etoposide and taxol.