Discovery of Carbono(di)thioates as Indoleamine 2,3-Dioxygenase 1 Inhibitors
| العنوان: | Discovery of Carbono(di)thioates as Indoleamine 2,3-Dioxygenase 1 Inhibitors |
|---|---|
| المؤلفون: | Shota Takeda, Hiroyuki Miyachi, Yukiko Mizumoto, Osamu Takikawa, Akira Asai, Miyuki Kumazawa, Kenji Matsuno, Minoru Waki, Miwa Fukuda, Osamu Ohno, Tomoko Hashimoto, Manabu Tejima, Kakeru Sato, Kenji Suzuki |
| المصدر: | ACS Med Chem Lett |
| بيانات النشر: | American Chemical Society (ACS), 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | biology, 010405 organic chemistry, Stereochemistry, Organic Chemistry, Active site, Alkaline hydrolysis (body disposal), 01 natural sciences, Biochemistry, 0104 chemical sciences, 010404 medicinal & biomolecular chemistry, chemistry.chemical_compound, chemistry, Docking (molecular), Drug Discovery, biology.protein, Indoleamine 2,3-dioxygenase, Cytotoxicity, Derivatization, Heme, Kynurenine |
| الوصف: | [Image: see text] A structure–activity relationship study unexpectedly showed that carbonothioates 4a and 4b, obtained by a unique alkaline hydrolysis of 2-alkylthio-oxazolines 3a and 3b, respectively, are a novel scaffold for indoleamine 2,3-dioxygenase 1 (IDO1) inhibitors. Derivatization of the carbonothioates enhanced inhibitory activity against IDO1 and cellular kynurenine production without cytotoxicity and led to the discovery of the related scaffolds carbonodithioates 5 and cyanocarbonimidodithioates 6 as IDO1 inhibitors. Incorporation of an OH group provided the most potent analogue 5i. UV–visible absorption spectroscopy of the Soret band, as well as docking and peptide mapping studies, suggested that these molecules bind to the heme in the active site of IDO1. Our unique IDO1 inhibitors are potential leads for future development. |
| تدمد: | 1948-5875 |
| DOI: | 10.1021/acsmedchemlett.0c00527 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9949b6c467e10644fac1483ac8891abc https://doi.org/10.1021/acsmedchemlett.0c00527 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....9949b6c467e10644fac1483ac8891abc |
| قاعدة البيانات: | OpenAIRE |
كن أول من يترك تعليقا!