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Novel Hybrid Molecules of Epinastine and Mefenamic Acid for Bioactive Assessment as Potential Anti‐inflammatory Agents
Author(s) -
Lee Ju Mi,
Damodar Kongara,
Lee Yeontaek,
Woo Hyeong Ryeol,
Suh Hong Won,
Jeon Sung Ho,
Lee Jeong Tae
Publication year - 2020
Publication title -
bulletin of the korean chemical society
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.237
H-Index - 59
ISSN - 1229-5949
DOI - 10.1002/bkcs.11990
Subject(s) - mefenamic acid , chemistry , in vitro , cytotoxicity , hybrid , biochemistry , nitric oxide , pharmacology , biology , botany , chromatography , organic chemistry
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 IC 50 values ranging in between 27.69 ± 3.06 and 40.19 ± 5.52 μM without notable cytotoxicity (CC 50 ≥ 100 μM) except 6 . Comparing the inhibitory effects, cytotoxicity and in vitro efficacy index ( i EI), 4 (IC 50 = 32.09 ± 4.04 μM; i EI = 6.23) and 7 (IC 50 = 27.69 ± 3.06 μM; i EI = 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.