H

Figure 7 Chemical structure of BN 80933, a dual inhibitor of lipid peroxidation and neuronal nitric oxide synthase (nNOS).58 The peroxidation-inhibiting chroman moiety works by donating an electron from the hydroxyl group to a lipid peroxyl radical.

with a moiety that will either inhibit 'NO production or scavenger peroxynitrite or peroxynitrite-derived radicals. Two examples of this approach are the 2-methylaminochroman U-78517F57 (Figure 2) and BN-8093358 (Figure 7). These new compound entities link the peroxyl radical scavenging chroman ring structure of vitamin E (Figure 2) via a piperazine bridge to the peroxyl radical scavenging amine moiety of tirilazad in the case of U-78517F, or with the an inhibitor nitric oxide synthase (NOS) in the case of BN-80933, which would decrease production of 'NO and consequently reduce peroxynitrite formation. U-78517F is more effective than either vitamin E or the vitamin E chroman in protecting culture spinal cord neurons from oxidative damage.57 Similarly, BN-80933 has greater neuroprotective activity than other single antioxidant mechanism new compound entities in rodent stroke and TBI models than either the trolox or NOS-inhibiting moieties alone.58

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