ABSTRACT
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 10 µM concentration and IC50 values are found in the range from 0.75 to 13.27 µM. 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.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/chemical synthesis , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Benzofurans/pharmacology , Nitric Oxide/antagonists & inhibitors , Animals , Anti-Inflammatory Agents, Non-Steroidal/chemistry , Benzofurans/chemical synthesis , Benzofurans/chemistry , Cell Line , Cell Proliferation/drug effects , Cell Survival/drug effects , Dose-Response Relationship, Drug , Lipopolysaccharides/antagonists & inhibitors , Lipopolysaccharides/pharmacology , Mice , Molecular Structure , Nitric Oxide/biosynthesis , Structure-Activity RelationshipABSTRACT
Piperlongumine (PL) and its derivatives were synthesized by the direct reaction between acid chloride of 3,4,5-trimethoxycinnamic acid and various amides/lactams. Later their anti-inflammatory effects were evaluated in lipopolysaccharide (LPS)-induced RAW-264.7 macrophages. Of the piperlogs prepared in this study, the maximum (91%) inhibitory activity was observed with PL (IC50=3 µM) but showed cytotoxicity whereas compound 3 (IC50=6 µM) which possess α,ß-unsaturated γ-butyrolactam moiety offered good level (65%) of activity with no cytotoxicity. This study revealed that amide/lactam moiety connected to cinnamoyl group with minimum 3 carbon chain length and α,ß-unsaturation is fruitful to show potent anti-inflammatory activity.
