| Autor: |
Vágvölgyi M; Institute of Pharmacognosy, Interdisciplinary Excellence Centre, University of Szeged, 6720 Szeged, Hungary., Girst G; Institute of Pharmacognosy, Interdisciplinary Excellence Centre, University of Szeged, 6720 Szeged, Hungary.; Institute of Pharmaceutical Chemistry, University of Szeged, 6720 Szeged, Hungary., Kúsz N; Institute of Pharmacognosy, Interdisciplinary Excellence Centre, University of Szeged, 6720 Szeged, Hungary., Ötvös SB; Institute of Pharmaceutical Chemistry, University of Szeged, 6720 Szeged, Hungary.; MTA-SZTE Stereochemistry Research Group, Hungarian Academy of Sciences, 6720 Szeged, Hungary., Fülöp F; Institute of Pharmaceutical Chemistry, University of Szeged, 6720 Szeged, Hungary.; MTA-SZTE Stereochemistry Research Group, Hungarian Academy of Sciences, 6720 Szeged, Hungary., Hohmann J; Institute of Pharmacognosy, Interdisciplinary Excellence Centre, University of Szeged, 6720 Szeged, Hungary.; Interdisciplinary Centre for Natural Products, University of Szeged, 6720 Szeged, Hungary., Servais JY; Department of Infection and Immunity, Luxembourg Institute of Health, L-4354 Esch-sur-Alzette, Luxemburg., Seguin-Devaux C; Department of Infection and Immunity, Luxembourg Institute of Health, L-4354 Esch-sur-Alzette, Luxemburg., Chang FR; Graduate Institute of Natural Products, Kaohsiung Medical University, Kaohsiung 807, Taiwan., Chen MS; Department of Biochemical Science and Technology, College of Life Science, National Taiwan University, Taipei City 10617, Taiwan., Chang LK; Department of Biochemical Science and Technology, College of Life Science, National Taiwan University, Taipei City 10617, Taiwan., Hunyadi A; Institute of Pharmacognosy, Interdisciplinary Excellence Centre, University of Szeged, 6720 Szeged, Hungary.; Interdisciplinary Centre for Natural Products, University of Szeged, 6720 Szeged, Hungary. |
| Abstrakt: |
Protoflavones, a rare group of natural flavonoids with a non-aromatic B-ring, are best known for their antitumor properties. The protoflavone B-ring is a versatile moiety that might be explored for various pharmacological purposes, but the common cytotoxicity of these compounds is a limitation to such efforts. Protoapigenone was previously found to be active against the lytic cycle of Epstein-Barr virus (EBV). Further, the 5-hydroxyflavone moiety is a known pharmacophore against HIV-integrase. The aim of this work was to prepare a series of less cytotoxic protoflavone analogs and study their antiviral activity against HIV and EBV. Twenty-seven compounds, including 18 new derivatives, were prepared from apigenin through oxidative de-aromatization and subsequent continuous-flow hydrogenation, deuteration, and/or 4'-oxime formation. One compound was active against HIV at the micromolar range, and three compounds showed significant activity against the EBV lytic cycle at the medium-low nanomolar range. Among these derivatives, protoapigenone 1'- O -isopropyl ether ( 6 ) was identified as a promising lead that had a 73-times selectivity of antiviral over cytotoxic activity, which exceeds the selectivity of protoapigenone by 2.4-times. Our results open new opportunities for designing novel potent and safe anti-EBV agents that are based on the natural protoflavone moiety. |
