دورية أكاديمية
Inhibition of LPS-Induced PGE2 Production by Arylsulfonamide Derivatives via the Selective Inhibition of mPGES-1 Enzyme
| العنوان: | Inhibition of LPS-Induced PGE2 Production by Arylsulfonamide Derivatives via the Selective Inhibition of mPGES-1 Enzyme |
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| المؤلفون: | Misong Kim, Changyoung Jang, Yunchan Nam, Kyung-Tae Lee, Jaeyeol Lee |
| المصدر: | Proceedings, Vol 22, Iss 1, p 37 (2019) |
| بيانات النشر: | MDPI AG, 2019. |
| سنة النشر: | 2019 |
| المجموعة: | LCC:General Works |
| مصطلحات موضوعية: | mPGES-1, inflammation, arylsulfonamides, General Works |
| الوصف: | Microsomal prostaglandin E synthase-1 (mPGES-1) is responsible for the massive prostaglandin E2 (PGE2) formation during inflammation. Increasing evidence reveals mPGES-1 inhibitors as a safe alternative to nonsteroidal anti-inflammatory drugs. Recently, we reported that a novel series of phenylsulfonyl hydrazide derivatives could reduce LPS-induced PGE2 levels in RAW 264.7 macrophage cells via an inhibition of the mPGES-1 enzyme. However, a few of the phenylsulfonyl hydrazide derivatives showed poor metabolic stability in liver microsomes. In order to identify new mPGES-1 inhibitors with improved metabolic stability, therefore, a series of arylsulfonamide derivatives has been synthesized and biologically evaluated against PGE2 production and the mPGES-1 enzyme. Among them, MPO-0186 inhibits the production of PGE2 (IC50 = 0.20 μM) in A549 cells via inhibition of mPGES-1 (IC50 = 0.49 μM in a cell-free assay) together with high selectivity over both COX-1 and COX-2. A molecular docking study theoretically suggests that MPO-0186 could inhibit PGE2 production by blocking the PGH2 binding site of the mPGES-1 enzyme. Furthermore, MPO-0186 demonstrated good metabolic stability in human liver microsomes and no significant inhibition observed in clinically relevant CYP isoforms. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2504-3900 20190220 |
| Relation: | https://www.mdpi.com/2504-3900/22/1/37; https://doaj.org/toc/2504-3900 |
| DOI: | 10.3390/proceedings2019022037 |
| URL الوصول: | https://doaj.org/article/328177c7897c4329853f6de3276e9640 |
| رقم الأكسشن: | edsdoj.328177c7897c4329853f6de3276e9640 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 25043900 20190220 |
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| DOI: | 10.3390/proceedings2019022037 |