Sidthipong Kulrawee, Ma Jun, Yu Wei Lin, Wang Yan Feng, Kobayashi Susumu, Kishino Satoshi, Koide Naoki, Yokochi Takashi, Kato Kuniki, Okada Shoshiro, Umezawa Kazuo
Department of Molecular Target Medicine, Aichi Medical University School of Medicine, 1-1 Yazako-Karimata, Nagakute 480-1195, Japan.
Shenzhen Wanhe Pharmaceutical Co., Ltd., Hi-tech Industrial Park, Nanshan District, Shenzhen, China.
Bioorg Med Chem Lett. 2017 Feb 1;27(3):562-566. doi: 10.1016/j.bmcl.2016.12.017. Epub 2016 Dec 8.
(-)-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.
（-）-去羟甲基环氧喹霉素（（-）-DHMEQ，1）是一种特异性的核因子κB（NF-κB）抑制剂。它通过其环氧基团与NF-κB组分特定半胱氨酸残基中的巯基结合，从而抑制DNA结合。在本研究中，我们设计并合成了一种无环氧类似物，称为（S）-β-水杨酰氨基-α-外向亚甲基-γ-丁内酯（SEMBL，3）。SEMBL在体外抑制NF-κB组分p65的DNA结合。它抑制脂多糖（LPS）诱导的NF-κB激活、诱导型一氧化氮合酶（iNOS）表达及炎性细胞因子分泌。它还抑制卵巢癌ES-2细胞中的NF-κB及细胞侵袭。此外，与（-）-DHMEQ相比，其在水溶液中的稳定性大大提高。因此，SEMBL有潜力成为一种新型抗炎和抗癌药物的候选物。
