Journal of the Korean Chemical Society (대한화학회지)

Korean Chemical Society (대한화학회)
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Discovery of Epinastine-NSAID Hybrids as Potential Anti-inflammatory Agents: Synthesis and In Vitro Nitric Oxide Production Inhibitory Activity Study

  • Woo, Hyeong Ryeol (Department of Chemistry and Institute of Applied Chemistry, Hallym University) ;
  • Damodar, Kongara (Department of Chemistry and Institute of Applied Chemistry, Hallym University) ;
  • Lee, Yeontaek (Department of Life Science and Multidisciplinary Genome Institute, Hallym University) ;
  • Lim, Soon-sung (Department of Food Science and Nutrition and Institute of Korean Nutrition, Hallym University) ;
  • Jeon, Sung Ho (Department of Life Science and Multidisciplinary Genome Institute, Hallym University) ;
  • Lee, Jeong Tae (Department of Chemistry and Institute of Applied Chemistry, Hallym University)
  • Received : 2019.12.30
  • Accepted : 2020.02.07
  • Published : 2020.04.20
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Abstract

A novel pharmacophore with epinastine (1) and NSAID moieties (2-5) was designed by molecular hybridization approach. The hybrid compounds 6-9 were synthesized by EDCI/HOBt or HATU-mediated coupling of 1 with salicylic acid (2), mefenamic acid (3), indomethacin (4) and naproxen (5), respectively, and were assessed for their inhibitory effect against NO production in LPS-induced RAW-264.7 macrophages in vitro. The Hybrids were found to exhibit significant NO production inhibitory effects with half-maximal inhibitory concentration (IC50) values ranging in between 15.96 ± 1.32 and 36.68 ± 2.53 μM and were non-cytotoxic to macrophages. Comparing the inhibition concentration (IC50), cytotoxicity concentration (CC50) and in vitro efficacy index (iEI), 6 (IC50 = 17.97 ± 1.92 μM; iEI = 11.13) and 9 (IC50 = 15.96 ± 1.32 μM; iEI = 12.53) were better suited than other hybrids as well as their parent compound. Our findings signify that hybrids 6 and 9 may serve as platforms for continued investigations for the development of more efficient anti-inflammatory agents.

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