Trienomycin A-simplified analogs: Synthesis and anti-neuroinflammatory activity

Bioorg Med Chem Lett. 2023 Jan 15:80:129122. doi: 10.1016/j.bmcl.2022.129122. Epub 2022 Dec 30.

Abstract

A series of novel trienomycin A (TA)-mimetic compounds (5a-p) have been designed, synthesized, and evaluated for their in vitro anti-neuroinflammatory and neuroprotective activities. Among them, compounds 5h, 5n, and 5o exhibits relatively strong NO inhibitory activity in LPS-activated BV-2 cells with the EC50 values of 12.4, 17.3, and 8.9 μM, respectively. Moreover, 5h showed evidently neuroprotective effect against H2O2-induced PC-12 cells without cytotoxicity at 20 μM. Overall, these compounds can provide a better understanding of the structure-activity relationship of TA and furnish research ideas for anti-neuroinflammatory and neuroprotective agents.

Keywords: NCxDA; Neuroinflammatory activity; Neuroprotective effect; Trienomycin A.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alanine
  • Animals
  • Hydrogen Peroxide* / pharmacology
  • Neuroprotective Agents* / pharmacology
  • PC12 Cells
  • Rats
  • Structure-Activity Relationship

Substances

  • Hydrogen Peroxide
  • trienomycin A
  • Alanine
  • Neuroprotective Agents