Novel Hybrid Molecules of Epinastine and Mefenamic Acid for Bioactive Assessment as Potential Anti‐inflammatory Agents

摘要

A set of novel epinastine (1) and mefenamic acid (2) hybrids (3–7) tethered via amide bond were designed and synthesized with the artistry of molecular hybridization. Then their inhibitory effect on nitric oxide (NO) production in LPS‐induced RAW‐264.7 macrophages and the expression levels of prostaglandin (PG) synthesis regulatory genes were evaluated in vitro. All the hybrids were found to have remarkable NO production inhibitory potential with IC50 values ranging in between 27.69?±?3.06 and 40.19?±?5.52?μM without notable cytotoxicity (CC50?≥?100?μM) except 6. Comparing the inhibitory effects, cytotoxicity and in vitro efficacy index (iEI), 4 (IC50 = 32.09?±?4.04?μM; iEI = 6.23) and 7 (IC50 = 27.69?±?3.06?μM; iEI = 6.40) were better suited than other hybrids as well as their parent compounds EH and MA. This outcome was further harmonized with the reduced microsomal prostaglandin E synthase‐1 expression and unaltered housekeeping COX‐1 expression by hybrids 4 and 7 treatment. Altogether, our findings signify that hybrids 4 and 7 may serve as platforms for continued investigations for the development of more efficient anti‐inflammatory agents.