Opa VajraguptaSuwanna ToasaksiriChantana BoonyaratYuvadee WongkrajangPenchom PeungvichaHiroshi WatanabePreecha BoonchoongMahidol UniversityUniversity of Toyama2018-09-072018-09-072000-01-01Free Radical Research. Vol.32, No.2 (2000), 145-155107157622-s2.0-0033967295https://repository.li.mahidol.ac.th/handle/123456789/25888A series of chroman amide and nicotinyl amide derivatives was designed and synthesized for the treatment of traumatic and ischemic CNS injury. Five compounds were significantly more potent inhibitors of lipid peroxidation in vitro than the reference antioxidant, trolox (p<0.01). Quantitative structure activity studies demonstrated that the inhibitory action was related to the ability to donate electrons, charge on hydroxy group and E(LUMO), to scavenging radicals and to the lipophilicity log P, which determines penetration of membrane lipids. ESR study indicated the ability, of 12 to scavenge the hydroxyl radicals. The most promising compound, [(3,4-dihydro-6- hydroxy-2,5,7,8-tetramethyl-2H-1-benzopyran-2yl)carbonyl]3'-(aminoethyl) indole (12), inhibited ex vivo lipid peroxidation in a head injury model and showed potent in vivo neuroprotective efficacy. Improvement of neurological recovery within 1 h of injury (grip test score) by as much as 200% was observed together with significant anti-anoxia activity. Compound 12 was a potent antagonist of methamphetamine-induced hypermotility resulting from dopamine release in the mouse brain. These results support the importance of cerebroprotective radical-scavenging agents for the treatment of traumatic injury and anoxia as well as provide additional evidence for the role of oxygen radicals and dopamine in brain damage.Mahidol UniversityBiochemistry, Genetics and Molecular BiologyArticleSCOPUS10.1080/10715760000300151