NITROAROMATIC AMINO-ACIDS AS INHIBITORS OF NEURONAL NITRIC-OXIDE SYNTHASE

Nitric oxide (NO .) is an important biomodulator of many physiological processes. The inhibition of inappropriate production of NO . by the isoforms of nitric oxide synthase (NOS) has been proposed as a therape utic approach for the treatment of stroke, inflammation, and other pro cesses. In this study, certain 2-nitroaryl-substituted amino acid anal ogues were discovered to inhibit NOS. Analogues bearing a 5-methyl sub stituent on the aromatic ring demonstrated maximal inhibitory potency. For two selected inhibitors, investigation of the kinetics of the enz yme showed the inhibition to be competitive with L-arginine. Additiona lly, functional NOS inhibition in tissue preparations was demonstrated .