1. Academic Validation
  2. Discovery of Coixol Derivatives as Potent Anti-inflammatory Agents

Discovery of Coixol Derivatives as Potent Anti-inflammatory Agents

  • J Nat Prod. 2023 Aug 25;86(8):1950-1959. doi: 10.1021/acs.jnatprod.3c00309.
Enjing Cui 1 Shihu Qian 1 Jiaming Li 1 2 3 Xueyang Jiang 1 2 3 4 Hongwei Wang 1 Shuaishuai Du 1 Le Du 1
Affiliations

Affiliations

  • 1 College of Pharmacy, Anhui University of Chinese Medicine, Hefei 230012, China.
  • 2 Deparment of Medicinal Chemistry, Anhui Academy of Chinese Medicine, Hefei 230012, China.
  • 3 Anhui Province Key Laboratory of Research & Development of Chinese Medicine, Hefei 230012, China.
  • 4 Department of Natural Medicinal Chemistry, China Pharmaceutical University, Nanjing 211198, China.
Abstract

Coixol, a derivative of 2-benzoxazolinone extracted from coix (Coix lachryma-jobi L. var. ma-yuen 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 (9c) or nitrofuran (9j) moieties displayed more pronounced activity than coixol and celecoxib. Mechanistic investigations revealed that 9c and 9j 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. In vivo studies confirmed the anti-inflammatory activity of 9c and 9j in a xylene-induced mice auricles edema model. The preliminary in vitro and in vivo research findings suggest that 9c and 9j have the potential to be developed as anti-inflammatory agents.

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