Synthesis of novel natural product-like diaryl acetylenes as hypoxia inducible factor-1 inhibitors and antiproliferative agents

论文类型：期刊论文

发表时间：2019-01-01

发表刊物：RSC ADVANCES

收录刊物：SCIE、EI

卷号：9

期号：24

页面范围：13878-13886

ISSN号：2046-2069

摘要：The selaginellin derivatives are a type of novel natural pigments with an unusual alkynyl phenol skeleton from the genus Selaginella. Some of these natural compounds were previously reported to show important bioactivities, including anticancer activity, cardiovascular protection and phosphodiesterase-4 inhibition. We designed and synthesized fifteen biphenyl-containing diaryl acetylene derivatives mimicking the skeleton of natural alkynyl phenols. In MTT assay in cancer cells, compounds 1c, 2d, 2g, 2h, 2i and 2j exhibited potent antiproliferative activity. The evaluation of Hypoxia Inducible Factor-1 (HIF-1) pathway inhibitory activity in dual luciferase assay demonstrated that most tested compounds exhibited moderate to good activities. Compounds 1a, 2f and 2h displayed high HIF-1 inhibitory activities and relatively low cytotoxicity, demonstrating great potential as HIF-1 inhibitors. These results afford a new strategy for the discovery of new HIF-1 inhibitors and anti-proliferative agents from natural or synthetic diaryl acetylene derivatives.