First synthesis of tabamides A-C and their derivatives: In vitro nitric oxide inhibitory activity

The first synthesis of natural phenolic amides, tabamides A-C (1-3), and their derivatives (4-12) was accomplished using Stobbe condensation and amide coupling reactions as key steps. The in vitro nitric oxide (NO) inhibitory effects of these compounds in LPS-induced RAW-264.7 macrophages were evaluated as an indicator of anti-inflammatory activity. All compounds tested had a concentration-dependent inhibitory effect on NO production by RAW-264.7 macrophages without significant cytotoxicity. Compound 6, a tabamide A derivative (IC50 = 82.6 mu M), followed by tabamide A (1, IC50 = 100.7 mu M), was the most potent from the series. The present study revealed that tabamide A (1) could be considered as a lead structure to develop NO production-targeted anti-inflammatory agents. (C) 2021 Elsevier Ltd. All rights reserved.