Rivière Solenne, Vielmuth Christin, Ennenbach Christiane, Abdelrahman Aliaa, Lemke Carina, Gütschow Michael, Müller Christa E, Menche Dirk
Kekulé-Institut für Organische Chemie und Biochemie, Universität Bonn, Gerhard-Domagk-Strasse 1, 53121, Bonn, Germany.
Pharmazeutische & Medizinische Chemie, Pharmazeutisches Institut, Universität Bonn, An der Immenburg 4, 53121, Bonn, Germany.
ChemMedChem. 2020 Jul 20;15(14):1348-1363. doi: 10.1002/cmdc.202000154. Epub 2020 Jun 10.
The archazolids are potent antiproliferative compounds that have recently emerged as a novel class of promising anticancer agents. Their complex macrolide structures and scarce natural supply make the development of more readily available analogues highly important. Herein, we report the design, synthesis and biological evaluation of four simplified and partially saturated archazolid derivatives. We also reveal important structure-activity relationship data as well as insights into the pharmacophore of these complex polyketides.
阿奇唑类化合物是一类具有强大抗增殖活性的化合物,最近作为一类有前景的新型抗癌药物崭露头角。它们复杂的大环内酯结构以及天然来源稀缺,使得开发更容易获得的类似物变得极为重要。在此,我们报道了四种简化的、部分饱和的阿奇唑衍生物的设计、合成及生物学评价。我们还揭示了重要的构效关系数据以及对这些复杂聚酮化合物药效团的见解。