Université Paris-Saclay, CNRS, BioCIS, 92290, Châtenay-Malabry, France.
Institut de Chimie des Substances Naturelles, UPR 2301, CNRS, avenue de la terrasse, 91198, Gif sur Yvette, France.
ChemMedChem. 2020 Aug 19;15(16):1571-1578. doi: 10.1002/cmdc.202000197. Epub 2020 Jun 24.
In this article, we report the synthesis and biological properties of a series of novel oxazepines related to isoCA-4 having significant antitumor properties. Among them, three oxazepin-9-ol derivatives display a nanomolar or a sub-nanomolar cytotoxicity level against five human cancer cell lines (HCT116, U87, A549, MCF7, and K562). It was demonstrated that the lead compound in this series inhibits tubulin assembly with an IC value of 1 μM and totally arrests the cellular cycle in the G2/M phase at the low concentration of 5 nM in HCT116 and K562 cells. Molecular modeling studies perfectly corroborates these promising results.
在本文中，我们报告了一系列与具有显著抗肿瘤特性的 isoCA-4 相关的新型噁唑烷的合成和生物学特性。其中，三种噁唑烷-9-醇衍生物对五种人类癌细胞系（HCT116、U87、A549、MCF7 和 K562）表现出纳摩尔或亚纳摩尔的细胞毒性水平。结果表明，该系列中的先导化合物以 1 μM 的 IC 值抑制微管组装，并在低浓度 5 nM 时完全将细胞周期阻滞在 HCT116 和 K562 细胞的 G2/M 期。分子建模研究完全证实了这些有希望的结果。
