Discovery of Coixol Derivatives as Potent Anti-inflammatory Agents

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.

Penifuranone A: A Novel Alkaloid from the Mangrove Endophytic Fungus Penicillium crustosum SCNU-F0006

“…The MTT method was utilized to assess cell viability [25][26][27]. RAW 264.7 cells, at a concentration of 5 × 10 5 cells/mL, were plated in 96-well plates and exposed to lipopolysaccharide (LPS, at 1 µg/mL) in the presence or absence of the test compounds for a duration of 24 h. Following this, 100 µL of a 2 mg/mL MTT solution was introduced into each well, and after a 4 h incubation, the resulting formazan precipitates were dissolved in 100 µL of DMSO.…”

“…Not only that, but persistent infection with pathogenic microorganisms can cause inflammatory response in various parts of the body [23,24]. Chronic or sustained inflammatory responses can cause tissue damage; potentially trigger acute inflammatory diseases such as acute gastroenteritis, bacteremia, toxemia, and acute 2 of 15 renal disease, as well as chronic diseases such as chronic nephritis, chronic hepatitis, chronic bronchitis, and cancer; or even result in death [25,26]. As a result, the pursuit of innovative drugs which exhibit enhanced efficacy and fewer side effects and effectively manage inflammatory diseases and microbial infection is crucial [27].…”

“…renal disease, as well as chronic diseases such as chronic nephritis, chronic chronic bronchitis, and cancer; or even result in death [25,26]. As a result, the innovative drugs which exhibit enhanced efficacy and fewer side effects and e manage inflammatory diseases and microbial infection is crucial [27].…”