Spirohypertones A and B as potent antipsoriatics: Tumor necrosis factor-α inhibitors with unprecedented chemical architectures

• DOI: 10.1016/j.apsb.2024.02.002
• Publication Date: 2024-02-20T07:42:12Z
• Authors: Yulin Duan; Weiguang Sun; Yongqi Li; Zhengyi Shi; Lanqin Li; Yeting Zhang; Kun Huang; Zhiping Zhang; Changxing Qi; Yonghui Zhang
• Keywords: HaCaT; Imiquimod

Tumor necrosis factor-α (TNF-α) is a promising target for inflammatory and autoimmune diseases. Spirohypertones A (1) B (2), two unprecedented polycyclic polyprenylated acylphloroglucinols with highly rearranged skeletons, were isolated from Hypericum patulum. The structures of 1 2 confirmed through comprehensive spectroscopic analysis, single-crystal X-ray diffraction electronic circular dichroism calculations. Importantly, showed remarkable TNF-α inhibitory activity, which could protect L929 cells death induced by co-incubation actinomycin D. It also demonstrated the ability to suppress response in HaCaT stimulated TNF-α. Notably, an imiquimod-induced psoriasis murine model, restrained symptoms epidermal hyperplasia associated psoriasis, presenting anti-inflammatory antiproliferative effects. This discovery positions as potent inhibitor, providing lead compound developing antipsoriatic agent.