Synthesis and biological evaluation of 2-aroylbenzofurans, rugchalcones A, B and their derivatives as potent anti-inflammatory agents

• Published in: Bioorganic & medicinal chemistry letters Vol. 26; no. 6; pp. 1521 - 1524
• Main Authors: Seo, Young Hwa, Damodar, Kongara, Kim, Jin-Kyung, Jun, Jong-Gab
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 15.03.2016; Elsevier
• Subjects: 2-Aroylbenzofuran; Animals; anti-Inflammatory; Anti-Inflammatory Agents, Non-Steroidal - chemical synthesis; Anti-Inflammatory Agents, Non-Steroidal - chemistry; Anti-Inflammatory Agents, Non-Steroidal - pharmacology; Benzofurans - chemical synthesis; Benzofurans - chemistry; Benzofurans - pharmacology; Cell Line; Cell Proliferation - drug effects; Cell Survival - drug effects; Chemistry; Chemistry, Medicinal; Chemistry, Organic; Dose-Response Relationship, Drug; Life Sciences & Biomedicine; Lipopolysaccharides - antagonists & inhibitors; Lipopolysaccharides - pharmacology; Mice; Molecular Structure; Nitric oxide; Nitric Oxide - antagonists & inhibitors; Nitric Oxide - biosynthesis; Pharmacology & Pharmacy; Physical Sciences; Rap–Stoermer reaction; Rugchalcones; Science & Technology; Structure-Activity Relationship; 2-Aroylbenzofuran; anti-Inflammatory; Rugchalcones; Nitric oxide; Rap–Stoermer reaction; INFLAMMATION; Rap-Stoermer reaction; BENZOFURAN
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2016.02.023

[Display omitted] An efficient synthesis of 2-aroylbenzofurans, rugchalcones A, B and their derivatives was accomplished in excellent yields by the Rap–Stoermer reaction between substituted salicylaldehydes and phenacyl bromides. Later their anti-inflammatory effects were evaluated in lipopolysaccharide (LPS)-induced RAW-264.7 macrophages. The compounds were exhibited exceptional potency against inflammatory mediated NO production with no cytotoxicity at 10μM concentration and IC50 values are found in the range from 0.75 to 13.27μM. Among the 2-aroylbenzofurans prepared in this study, compounds 4 (99.6%; IC50=0.57), rugchalcone B (2) (99.3%; IC50=4.13), 7 (96.8%; IC50=1.90) and 8 (74.3%; IC50=0.99) were showed the maximum inhibitory activity. This study suggests that compounds 2, 4, 7 and 8 which are having 4-hydroxyphenyl group and/or hydroxy (–OH) group at 5- and/or 6-position of benzofuran motif could be considered as a promising scaffolds for the further development of iNOS inhibitors for potential anti-inflammatory applications.