Title:QSAR Studies of Nitric Oxide Synthase Inhibitors
Volume: 23
Issue: 29
Author(s): Ioanna-Chrysoula Tsopka and Dimitra Hadjipavlou-Litina*
Affiliation:
- Department of Pharmaceutical Chemistry, School of Pharmacy, Faculty of Health Sciences, Aristotle University of
Thessaloniki, 54124, Thessaloniki, Greece
Keywords:
Nitric oxide (NO), NOS inhibitors, Pharmacophore modeling, QSAR, Hydrophobicity, Bulkiness.
Abstract:
Background: Nitric oxide is a free radical bioregulator controlling homeostasis, vasodilation,
and inhibition of platelet aggregation, significantly implicated in the nervous and immune
system functionality. In vivo it is produced by nitric oxide synthases (NOSs).
Objective: Overproduction of nitric oxide is linked to several inflammatory, immunological, and
neurodegenerative diseases and for that, various compounds have been synthesized as inhibitors
of NOSs. In this review, the QSAR analyses were summarized in a variety of compounds as potent
inhibitors of NOSs, and the models derived through 1D, 2D and 3D QSAR analyses.
Conclusion: Ten groups of various NOS inhibitors and 17 1D, 2D, and 3D QSAR models and
analyses were presented and discussed. A lack of hydrophobic terms was noticed in most of the
cases. Chemical substituents were selected considering the increase either of the hydrophilicity
and/or of hydrophobicity, bulkiness supported steric interactions, and point to potent inhibitors.
CMR (Calculated Molar Refractivity) a steric variable, with a negative sign, underlines the critical
effects participating on (in) an active site on the enzymes. Indicator variables imply the influence
of specific structural moieties. Electronic parameters were found to be significant.
