Antioxidative and anti-inflammatory activity of psiguadial B and its halogenated analogues as potential neuroprotective agents

  • Bioorg Chem. 2021 Aug:113:105027. doi: 10.1016/j.bioorg.2021.105027.
Tara Man Kadayat  1 ,  Dong Eun Kim  2 ,  Sang Bong Lee  3 ,  Kyungjin Jung  1 ,  Sang Eun Park  2 ,  Ji-Ye Hong  2 ,  Jina Kim  1 ,  Aarajana Shrestha  1 ,  Dong-Su Kim  4 ,  Hongchan An  1 ,  Nayeon Kim  1 ,  Su-Jeong Lee  1 ,  Sugyeong Kwon  1 ,  Suhui Kim  1 ,  Jun Yeon Hwang  1 ,  Shinae Kim  1 ,  Dongyup Hahn  5 ,  Hyukjae Choi  6 ,  Sang-Jip Nam  7 ,  Yong Hyun Jeon  8 ,  Jung Jin Hwang  9 ,  Sung Jin Cho  10 ,  Jungwook Chin  11
Affiliations
  • 1. New Drug Development Center, Daegu-Gyeongbuk Medical Innovation Foundation, Daegu 41061, Republic of Korea.
  • 2. Asan Institute for Life Sciences, Asan Medical Center, Seoul 05505, Republic of Korea.
  • 3. Vaccine Commercialization Center, Gyeongbuk Institute for Bio Industry, Andong 33618, Republic of Korea.
  • 4. Therapeutics and Biotechnology Division, Korea Research Institute of Chemical Technology, 34114 Daejeon, Republic of Korea.
  • 5. School of Food Science and Biotechnology, Kyungpook National University, Daegu 41566, Republic of Korea.
  • 6. College of Pharmacy, Yeungnam University, Gyeongbuk 38541, Republic of Korea.
  • 7. Department of Chemistry and Nanoscience, Ewha Womans University, Seoul 03760, Republic of Korea.
  • 8. Laboratory Animal Center, Daegu-Gyeongbuk Medical Innovation Foundation, Daegu 41061, Republic of Korea.
  • 9. Asan Institute for Life Sciences, Asan Medical Center, Seoul 05505, Republic of Korea; Department of Convergence Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea. Electronic address: [email protected].
  • 10. Convergence Research Center for Diagnosis, Treatment and Care System of Dementia, Korea Institute of Science and Technology, Seoul 02792, Republic of Korea. Electronic address: [email protected].
  • 11. New Drug Development Center, Daegu-Gyeongbuk Medical Innovation Foundation, Daegu 41061, Republic of Korea. Electronic address: [email protected].
PMID: 34098398 DOI: 10.1016/j.bioorg.2021.105027
Abstract

Psiguadial B (8), and its fluoro- (8a), chloro- (8b), and bromo- (8c) derivatives were synthesized using a sodium acetate-catalyzed single step coupling of three components: β-caryophyllene (5), diformylphloroglucinol (11), and benzaldehyde (12). These compounds efficiently and dose-dependently decreased H2O2-induced cell death, a quantitative marker of cell death, in primary cultures of mouse cortical neurons. Psiguadial B also decreased neuronal death and accumulation of ROS induced by FeCl2 in cortical cultures. The in vitro effects of these compounds in lipopolysaccharide (LPS)-induced expression of nitric oxide (NO), and TNF-α and IL-6 by suppressing the NF-κB pathway in immune cells demonstrated their antioxidative and anti-inflammatory activity. The present findings warrant further research on the development of psiguadial B-based neuroprotective agents for the treatment of neurodegenerative diseases, acute brain injuries and immunological disorders.

Keywords
Anti-inflammatory effect; Antioxidative effect; Neuroprotective agent; Psiguadial B; Reactive oxygen species; Short synthetic route.
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