[논문]Discovery of Epinastine-NSAID Hybrids as Potential Anti-inflammatory Agents: Synthesis and In Vitro Nitric Oxide Production Inhibitory Activity Study

Woo, Hyeong Ryeol; Damodar, Kongara; Lee, Yeontaek; Lim, Soon-sung; Jeon, Sung Ho; Lee, Jeong Tae

doi:10.5012/jkcs.2020.64.2.79

Discovery of Epinastine-NSAID Hybrids as Potential Anti-inflammatory Agents: Synthesis and In Vitro Nitric Oxide Production Inhibitory Activity Study 원문보기

대한화학회지 = Journal of the Korean Chemical Society, v.64 no.2, 2020년, pp.79 - 83

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)

Abstract ▼ AI-Helper

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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표/그림 (3)

그림 Figure 1. Structures of epinastine (1), salicylic acid (2), mefenamic acid (3), indomethacin (4), naproxen (5) and epinastine-NSAID hybrid compounds (6–9).
그림 Scheme 1. Synthesis of epinastine-NSAID hybrids 6–9.
표 Table 1. NO production inhibitory effects of epinastine-NSAID hybrids 6–9

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제안 방법

In this work, we designed and synthesized a series of hybrid compounds (6–9) of epinastine (1)-NSAID (2–5) as novel anti-inflammatory agents.

참고문헌 (15)

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