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Indexed by:Journal Papers

Date of Publication:2019-08-15

Journal:BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Included Journals:SCIE、PubMed

Volume:29

Issue:16

Page Number:2327-2331

ISSN No.:0960-894X

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

Abstract: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.