Jejucarbazoles A-C, carbazole glycosides with indoleamine 2,3-dioxygenase 1 inhibitory activity from Streptomyces sp. KCB15JA151

Jejucarbazoles AC,具有吲哚胺 2,3-双加氧酶 1 抑制活性的咔唑糖苷,来自链霉菌属 KCB15JA151

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作者:Gil Soo Kim, Jun-Pil Jang, Mincheol Kwon, Tae Hoon Oh, Kyung Taek Heo, Byeongsan Lee, Jung-Sook Lee, Sung-Kyun Ko, Young-Soo Hong, Jong Seog Ahn, Jae-Hyuk Jang

Abstract

A bioassay-guided investigation led to the isolation of three new carbazole glycosides, jejucarbazoles A-C (1-3), from Streptomyces sp. KCB15JA151. Their planar structures were elucidated by detailed NMR and MS spectroscopic analysis with a literature study. Their relative and absolute configurations were established by ROESY correlations, coupling constants, LC-MS analysis of thiocarbamoyl-thiazolidine carboxylate derivatives, and ECD calculation. Compounds 1-3 showed indoleamine 2,3-dioxygenase 1 (IDO1) inhibitory activity with IC50 values of 18.38, 9.17, and 8.81 μM. The molecular docking analysis suggested that all compounds act as heme-displacing inhibitors against IDO1 enzyme.

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