Synthesis and bioactivity of isoflavones from ficus carica and some non-natural analogues
- FicucariconeD (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 naturalproducts were, for the first time, obtained by chemical synthesisin six steps, starting from 2,4,6-trihydroxyacetophenone. Key stepsare a microwave-promoted tandem sequence of Claisen- and Cope-rearrangementsto install the 6-prenyl substituent and a Suzuki-Miyaura crosscoupling for installing the B-ring. By using various boronic acids,non-natural analogues become conveniently available. All compoundswere tested for cytotoxicity against drug-sensitive and drug-resistanthuman leukemia cell lines, but were found to be inactive. The compoundswere also tested for antimicrobial activities against a panel of eightGram-negative and two Gram-positive bacterial strains. Addition ofthe efflux pump inhibitor phenylalanine-arginine-beta-naphthylamide(PA beta N) significantly improved the antibiotic activity in mostcases, with MIC values as low as 2.5 mu M and activityFicucariconeD (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 naturalproducts were, for the first time, obtained by chemical synthesisin six steps, starting from 2,4,6-trihydroxyacetophenone. Key stepsare a microwave-promoted tandem sequence of Claisen- and Cope-rearrangementsto install the 6-prenyl substituent and a Suzuki-Miyaura crosscoupling for installing the B-ring. By using various boronic acids,non-natural analogues become conveniently available. All compoundswere tested for cytotoxicity against drug-sensitive and drug-resistanthuman leukemia cell lines, but were found to be inactive. The compoundswere also tested for antimicrobial activities against a panel of eightGram-negative and two Gram-positive bacterial strains. Addition ofthe efflux pump inhibitor phenylalanine-arginine-beta-naphthylamide(PA beta N) significantly improved the antibiotic activity in mostcases, with MIC values as low as 2.5 mu M and activity improvementfactors as high as 128-fold.…
Verfasserangaben: | Vaderament-Alexe Nchiozem-NgnitedemORCiD, Eric SperlichORCiDGND, Valaire Yemene Matieta, Jenifer Reine Ngnouzouba KueteORCiD, Victor KueteORCiD, Ejlal A. A. Omer, Thomas Efferth, Bernd SchmidtORCiDGND |
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DOI: | https://doi.org/10.1021/acs.jnatprod.3c00219 |
ISSN: | 0163-3864 |
ISSN: | 1520-6025 |
Pubmed ID: | https://pubmed.ncbi.nlm.nih.gov/37253120 |
Titel des übergeordneten Werks (Englisch): | Journal of natural products : Lloydia |
Verlag: | American Chemical Society |
Verlagsort: | Washington, DC |
Publikationstyp: | Wissenschaftlicher Artikel |
Sprache: | Englisch |
Datum der Erstveröffentlichung: | 30.05.2023 |
Erscheinungsjahr: | 2023 |
Datum der Freischaltung: | 13.05.2024 |
Freies Schlagwort / Tag: | Antimicrobial activity; Bacteria; Ethers; Flavonoids; Mixtures |
Band: | 86 |
Ausgabe: | 6 |
Seitenanzahl: | 9 |
Erste Seite: | 1520 |
Letzte Seite: | 1528 |
Fördernde Institution: | German Academic Exchange Service (DAAD); University of Potsdam;; Organization for the Prohibition of Chemical Weapons (OPCW) |
Organisationseinheiten: | Mathematisch-Naturwissenschaftliche Fakultät / Institut für Chemie |
DDC-Klassifikation: | 5 Naturwissenschaften und Mathematik / 54 Chemie / 540 Chemie und zugeordnete Wissenschaften |
Peer Review: | Referiert |