Withania somnifera phytochemicals confer neuroprotection by selective inhibition of nNos: An in silico study to search potent and selective inhibitors for human nNOS

Neuronal nitric oxide synthase (nNOS or NOS1) is an important therapeutic target for the treatment of various neurological diseases. A major challenge faced in the design of nNOS inhibitors emphasizes on potency in humans and selectivity over other NOS isoforms - eNOS and iNOS. The present structural-based in silico study was carried out to search potent and selective inhibitor for human nNOS from a set of 40 Withania somnifera phytochemicals structure. Ten phytochemicals appear as dual-selective inhibitors of nNOS over both iNOS and eNOS. Here we report five potent and selective human nNOS inhibitors, namely, Chlorogenic Acid, Withanolide B, Withacnistin Pelletierine, and Calystegine B2 based on their selectivity, binding energy and nNOS active site residues interaction profile. These phytochemicals have nNOS selectivity higher than 4-methyl-6-(2-(5-(3-(methylamino)propyl)pyridin-3-yl)-ethyl)pyridin-2-amine inhibitor and have potential as an oral neurotherapeutic agent to combat neurological disorders mediated by nNOS activation.