| Autor: |
Nchiozem-Ngnitedem VA; Institut für Chemie, University of Potsdam, Karl-Liebknecht-Strasse 24-25, D-14476 Potsdam-Golm, Germany., Sperlich E; Institut für Chemie, University of Potsdam, Karl-Liebknecht-Strasse 24-25, D-14476 Potsdam-Golm, Germany., Matieta VY; Department of Biochemistry, Faculty of Science, University of Dschang, Dschang, Cameroon., Ngnouzouba Kuete JR; Department of Chemistry, Faculty of Science, University of Dschang, Dschang, Cameroon., Kuete V; Department of Biochemistry, Faculty of Science, University of Dschang, Dschang, Cameroon., Omer EA; Department of Pharmaceutical Biology, Institute of Pharmaceutical and Biomedical Sciences, Johannes Gutenberg University, Staudinger Weg 5, 55128 Mainz, Germany., Efferth T; Department of Pharmaceutical Biology, Institute of Pharmaceutical and Biomedical Sciences, Johannes Gutenberg University, Staudinger Weg 5, 55128 Mainz, Germany., Schmidt B; Institut für Chemie, University of Potsdam, Karl-Liebknecht-Strasse 24-25, D-14476 Potsdam-Golm, Germany. |
| Abstrakt: |
Ficucaricone D ( 1 ) and its 4'-demethyl congener 2 are isoflavones isolated from fruits of Ficus carica 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. |
