Quantitative Structure-Activity Relationship Studies on Nitric Oxide Synthase Inhibitors

Abstract

It has been observed that the overproduction of Nitric Oxide (NO) causes disfunction of several organs and affects lactate level. Hence, attempts have been made to design and develop potent inhibitors for Nitric Oxide Synthases (NOSs), the enzymes which are responsible for its production. NOSs exist mainly in three different isoforms: neuronal, inducible, and endothelial, designated as nNOS, iNOS, and eNOS, respectively. For design and development of potent NOS inhibitors against all the 3 isoforms several Quantitative Structure-Activity Relationship (QSAR) studies were made. This article compiles comprehensively all such studies and discusses critically their outcome. For the inhibitors of all isoforms, some pharmacophore models have been developed in which commonly at least one H-bond donor, one H-bond acceptor, one hydrophobic group, and in some positively charged moieties have been found to be essential. Consistent to these pharmacophores, 2D and 3D QSAR studies have pointed out that all NOS inhibitors undergo H-bond, hydrophobic, electronic and steric interactions with the receptors. Keywords: Nitric oxide synthase inhibitors, quantitative structure-activity relationships.