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

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.