Synthesis, p38 α MAP kinase inhibition, anti‐inflammatory activity, and molecular docking studies of 1,2,4‐triazole‐based benzothiazole‐2‐amines

Abstract Recent studies have demonstrated that inhibition of p38α MAP kinase could effectively inhibit pro‐inflammatory cytokines including TNF‐α and interleukins. Thus, inhibition of this enzyme can prove greatly beneficial in the therapy of chronic inflammatory diseases. A new series of N‐[3‐(substituted‐4H‐1,2,4‐triazol‐4‐yl)]‐benzo[d]thiazol‐2‐amines (4a–n) were synthesized and subjected to in vitro evaluation for anti‐inflammatory activity (BSA anti‐denaturation assay) and p38α MAPK inhibition. Among the compounds selected for in vivo screening of anti‐inflammatory activity (4b, 4c, 4f, 4g, 4j, 4m, and 4n), compound 4f was found to be the most active with an in vivo anti‐inflammatory efficacy of 85.31% when compared to diclofenac sodium (83.68%). It was also found to have a low ulcerogenic risk and a protective effect on lipid peroxidation. The p38α MAP kinase inhibition of this compound (IC50 = 0.036 ± 0.12 μM) was also found to be superior to the standard SB203580 (IC50 = 0.043 ± 0.27 μM). Furthermore, the in silico binding mode of the compound on docking against p38α MAP kinase exemplified stronger interactions than those of SB203580. A new series N‐[3‐(substituted‐4H‐1,2,4‐triazol‐4‐yl)]benzo[d]thiazol‐2‐amines (4a–n) were synthesized and evaluated for anti‐inflammatory and p38α MAPK inhibitory activity. Compound 4f was found to be the most potent anti‐inflammatory agent, with lo...
Source: Archiv der Pharmazie - Category: Drugs & Pharmacology Authors: Tags: FULL PAPER Source Type: research