Duan Yulin, Sun Weiguang, Li Yongqi, Shi Zhengyi, Li Lanqin, Zhang Yeting, Huang Kun, Zhang Zhiping, Qi Changxing, Zhang Yonghui
Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Department of Pharmacy, Wuhan No. 1 Hospital, Wuhan 430022, China.
Acta Pharm Sin B. 2024 Jun;14(6):2646-2656. doi: 10.1016/j.apsb.2024.02.002. Epub 2024 Feb 20.
Tumor necrosis factor- (TNF-) is a promising target for inflammatory and autoimmune diseases. Spirohypertones A () and B (), two unprecedented polycyclic polyprenylated acylphloroglucinols with highly rearranged skeletons, were isolated from . The structures of and were confirmed through comprehensive spectroscopic analysis, single-crystal X-ray diffraction and electronic circular dichroism calculations. Importantly, showed remarkable TNF- inhibitory activity, which could protect L929 cells from death induced by co-incubation with TNF- and actinomycin D. It also demonstrated the ability to suppress the inflammatory response in HaCaT cells stimulated with TNF-. Notably, in an imiquimod-induced psoriasis murine model, restrained symptoms of epidermal hyperplasia associated with psoriasis, presenting anti-inflammatory and antiproliferative effects. This discovery positions as a potent TNF- inhibitor, providing a promising lead compound for developing an antipsoriatic agent.
肿瘤坏死因子-α（TNF-α）是炎症性和自身免疫性疾病的一个有前景的靶点。从[来源未提及]中分离出了螺旋高酮A（[具体结构未给出]）和B（[具体结构未给出]），这两种具有高度重排骨架的前所未有的多环多异戊烯基化酰基间苯三酚。通过全面的光谱分析、单晶X射线衍射和电子圆二色性计算确定了A和B的结构。重要的是，A显示出显著的TNF-α抑制活性，可保护L929细胞免受与TNF-α和放线菌素D共同孵育诱导的死亡。它还表现出抑制TNF-α刺激的HaCaT细胞中炎症反应的能力。值得注意的是，在咪喹莫特诱导的银屑病小鼠模型中，A抑制了与银屑病相关的表皮增生症状，呈现出抗炎和抗增殖作用。这一发现将A定位为一种有效的TNF-α抑制剂，为开发抗银屑病药物提供了一个有前景的先导化合物。
