Rational design, synthesis and in vitro evaluation of novel exo-methylene butyrolactone salicyloylamide as NF-κB inhibitor
| Autor: | Kazuo Umezawa, Susumu Kobayashi, K. Kato, Naoki Koide, Takashi Yokochi, Wei Lin Yu, Satoshi Kishino, Kulrawee Sidthipong, Jun Ma, Shoshiro Okada, Yan Feng Wang |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Lipopolysaccharides medicine.medical_treatment Clinical Biochemistry Pharmaceutical Science Epoxide 01 natural sciences Biochemistry 03 medical and health sciences chemistry.chemical_compound Mice Structure-Activity Relationship 4-Butyrolactone Cell Line Tumor Drug Discovery Salicylamides medicine Moiety Animals Humans Molecular Biology Dose-Response Relationship Drug Molecular Structure 010405 organic chemistry Macrophages Organic Chemistry Anti-Inflammatory Agents Non-Steroidal Rational design NF-kappa B NF-κB In vitro 0104 chemical sciences 030104 developmental biology Cytokine RAW 264.7 Cells chemistry Drug Design Molecular Medicine DNA Cysteine |
| Zdroj: | Bioorganicmedicinal chemistry letters. 27(3) |
| ISSN: | 1464-3405 |
| Popis: | (-)-Dehydroxymethylepoxyquinomicin ((-)-DHMEQ, 1) is a specific inhibitor of NF-κB. It binds to SH group in the specific cysteine residue of NF-κB components with its epoxide moiety to inhibit DNA binding. In the present research, we have designed and synthesized an epoxide-free analog called (S)-β-salicyloylamino-α-exo-methylene-ƴ-butyrolactone (SEMBL, 3). SEMBL inhibited DNA binding of NF-κB component p65 in vitro. It inhibited LPS-induced NF-κB activation, iNOS expression, and inflammatory cytokine secretions. It also inhibited NF-κB and cellular invasion in ovarian carcinoma ES-2 cells. Moreover, its stability in aqueous solution was greatly enhanced compared with (-)-DHMEQ. Thus, SEMBL has a potential to be a candidate for a new anti-inflammatory and anticancer agent. |
| Databáze: | OpenAIRE |
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