Synthesis and Bioactivity of Isoflavones from <i>Ficus carica</i> and Some Non-Natural Analogues
Vaderament‐A. Nchiozem‐Ngnitedem, Eric Sperlich, Valaire Yemene Matieta, Jenifer R. N. Kuete, Victor Kuete, Ejlal A. Omer, Thomas Efferth, Bernd Schmidt
Abstract
that share a 5,7-dimethoxy-6-prenyl-substituted A-ring. Both natural products were, for the first time, obtained by chemical synthesis in six steps, starting from 2,4,6-trihydroxyacetophenone. Key steps are a microwave-promoted tandem sequence of Claisen- and Cope-rearrangements to install the 6-prenyl substituent and a Suzuki-Miyaura cross coupling for installing the B-ring. By using various boronic acids, non-natural analogues become conveniently available. All compounds were tested for cytotoxicity against drug-sensitive and drug-resistant human leukemia cell lines, but were found to be inactive. The compounds were also tested for antimicrobial activities against a panel of eight Gram-negative and two Gram-positive bacterial strains. Addition of the efflux pump inhibitor phenylalanine-arginine-β-naphthylamide (PAβN) significantly improved the antibiotic activity in most cases, with MIC values as low as 2.5 μM and activity improvement factors as high as 128-fold.