College of Pharmacy, Anhui University of Chinese Medicine, Hefei 230012, China.
Deparment of Medicinal Chemistry, Anhui Academy of Chinese Medicine, Hefei 230012, China.
J Nat Prod. 2023 Aug 25;86(8):1950-1959. doi: 10.1021/acs.jnatprod.3c00309. Epub 2023 Aug 10.
Coixol, a derivative of 2-benzoxazolinone extracted from coix ( L. var. Stapf), has demonstrated promising anti-inflammatory activity and low cytotoxicity. In this study, 26 coixol derivatives were designed and synthesized by hybridization with cinnamic acid to identify new anti-inflammatory agents. The anti-inflammatory activities of the derivatives were screened using LPS-induced overexpression of nitric oxide (NO) in RAW264.7 macrophages. On the basis of the screening results, compounds containing furan () or nitrofuran () moieties displayed more pronounced activity than coixol and celecoxib. Mechanistic investigations revealed that and suppressed the expression of induced nitric oxide synthase (iNOS), tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1β, which was associated with the inhibition of the nuclear factor (NF)-κB signaling pathway. studies confirmed the anti-inflammatory activity of and in a xylene-induced mice auricles edema model. The preliminary and research findings suggest that and have the potential to be developed as anti-inflammatory agents.
来源于薏苡（L. var. Stapf）的 2-苯并恶唑酮衍生物 Coixol 具有显著的抗炎活性和低细胞毒性。本研究通过肉桂酸杂交设计和合成了 26 种 Coixol 衍生物，以鉴定新型抗炎剂。通过 LPS 诱导 RAW264.7 巨噬细胞中一氧化氮（NO）的过表达筛选衍生物的抗炎活性。基于筛选结果，含有呋喃（）或硝呋喃（）部分的化合物比 Coixol 和塞来昔布显示出更显著的活性。机制研究表明，和抑制诱导型一氧化氮合酶（iNOS）、肿瘤坏死因子（TNF）-α、白细胞介素（IL）-6 和 IL-1β 的表达，与核因子（NF）-κB 信号通路的抑制有关。在二甲苯诱导的小鼠耳廓水肿模型中进行的进一步体内研究证实了和的抗炎活性。初步的和药代动力学研究结果表明，和具有开发为抗炎剂的潜力。
