CF₃-Substituted Mollugin 2-(4-Morpholinyl)-ethyl ester as a Potential Anti-inflammatory Agent with Improved Aqueous Solubility and Metabolic Stability

• Published in: Molecules (Basel, Switzerland) Vol. 23; no. 8; p. 2030
• Main Authors: Hong, Ki Bum, Kim, Darong, Kim, Bo-Kyung, Woo, Seo Yeon, Lee, Ji Hoon, Han, Seung-Hee, Bae, Gyu-Un, Kang, Soosung
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 14-08-2018; MDPI
• Subjects: Adhesion; Adhesion tests; ADME; Animals; Anti-Inflammatory Agents - chemical synthesis; Anti-Inflammatory Agents - chemistry; Anti-Inflammatory Agents - pharmacology; Biological Availability; Cell adhesion; Cell adhesion & migration; Cell Adhesion - drug effects; Colon; Drug Stability; Epithelial cells; Esters - chemical synthesis; Esters - chemistry; Esters - pharmacology; Herbal medicine; HT29 Cells; Humans; Inflammation; inflammatory bowel disease; Interleukin 6; Metabolism; Mice; Molecular Structure; mollugin; Monocytes; Pyrans - chemical synthesis; Pyrans - chemistry; Pyrans - pharmacology; Solubility; Stability; Substitutes; Tumor necrosis factor-α; U937 Cells; solubility; ADME; inflammatory bowel disease; mollugin
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules23082030

Although mollugin, the main ingredient of the oriental medicinal herb
has considerable anti-inflammatory effects, it has poor aqueous solubility as well as poor metabolic and plasma stability. To overcome these shortfalls, various mollugin derivatives have been synthesized and evaluated for their ability to inhibit U937 monocyte cell adhesion to HT-29 colonic epithelial cells in TNF-α- or IL-6-induced models of colon inflammation. The 2-(4-morpholinyl)-ethyl ester of CF3-substituted mollugin (compound
) showed good water solubility, improved metabolic and plasma stability, and greater inhibitory activity than mesalazine in both the TNF-α- and IL-6-induced colonic epithelial cell adhesion assays, suggesting that
is a potential anti-inflammatory agent.