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发布时间：2019-11-06

论文类型：期刊论文

发表时间：2019-08-15

发表刊物：BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

收录刊物：PubMed、SCIE

卷号：29

期号：16

页面范围：2327-2331

ISSN号：0960-894X

关键字：Anti-tumor; Hypoxia inducible factor (HIF)-1; Marine alkaloids; Neolamellarin A; Structure-activity relationship

摘要：The novel marine pyrrole alkaloid neolamellarin A derived from sponge has been shown to inhibit hypoxia-induced HIF-1 activity. In this work, we designed and synthesized neolamellarin A and its series of derivatives by a convergent synthetic strategy. The HIF-1 inhibitory activity and cytotoxicity of these compounds were evaluated in Hela cells by dual-luciferase reporter gene assay and MIT assay, respectively. The results showed that neolamellarin A 1 (IC50 = 10.8 +/- 1.0 mu M) and derivative 2b (IC50 = 11.9 +/- 3.6 mu M) had the best HIF-1 inhibitory activity and low cytotoxicity. Our SAR research focused on the effects of key regions aliphatic carbon chain length, aromatic ring substituents and C-7 substituent on biological activity, providing a basis for the subsequent research on the development of novel pyrrole alkaloids as HIF-1 inhibitors and design of small molecule probes for target protein identification.