Synthesis and anti-neuroinflammatory activity of N-heterocyclic analogs based on natural biphenyl-neolignan honokiol

  • Bioorg Med Chem Lett. 2019 Jan 15;29(2):329-333. doi: 10.1016/j.bmcl.2018.11.014.
Yue Yuan  1 ,  Lalita Subedi  1 ,  Daesung Lim  1 ,  Jae-Kyung Jung  2 ,  Sun Yeou Kim  3 ,  Seung-Yong Seo  4
Affiliations
  • 1. College of Pharmacy, and Gachon Institute of Pharmaceutical Sciences, Gachon University, Incheon 21936, Republic of Korea.
  • 2. College of Pharmacy, Chungbuk National University, Cheongju, Chungbuk 28644, Republic of Korea.
  • 3. College of Pharmacy, and Gachon Institute of Pharmaceutical Sciences, Gachon University, Incheon 21936, Republic of Korea. Electronic address: [email protected].
  • 4. College of Pharmacy, and Gachon Institute of Pharmaceutical Sciences, Gachon University, Incheon 21936, Republic of Korea. Electronic address: [email protected].
PMID: 30472026 DOI: 10.1016/j.bmcl.2018.11.014
Abstract

Novel isoxazole and pyrazole analogs based on natural biphenyl-neolignan honokiol were synthesized and evaluated for their inhibitory activities against nitric oxide production in lipopolysaccharide-activated BV-2 microglial cells. The isoxazole skeleton was constructed via nitrile oxide cycloaddition from oxime 3 and pyrazole was generated by condensation of 4-chromone and alkylhydrazine. Among the analogs, 13b and 14a showed stronger inhibitory activities with IC50 values of 8.9 and 1.2 µM, respectively, than honokiol.

Keywords
Anti-neuroinflammatory activity; Biphenyl-neolignan; Honokiol; Isoxazole; Pyrazole.