Research Article
E-Pharmacophore Model Assisted Discovery of Novel Antagonists of
nNOS
Author(s): Nalamolu Ravina Madhulitha, Natarajan Pradeep, Swargam Sandeep, Kanipakam Hema, Pasala Chiranjeevi, Katari Sudheer Kumar and Amineni Uma-MaheswariNalamolu Ravina Madhulitha, Natarajan Pradeep, Swargam Sandeep, Kanipakam Hema, Pasala Chiranjeevi, Katari Sudheer Kumar and Amineni Uma-Maheswari
The nitric oxide (NO) synthesized by neuronal nitric oxide synthase (nNOS) acts as a neurotransmitter and plays a crucial role in a series of neurobiological functions. In diseased condition, activated nNOS induces nitrosylation as well as phosphorylation of tau protein and glycogen synthase kinase 3 beta (GSK-3β) respectively. Hyper phosphorylation of tau accelerates tau oligomerization resulting in formation of neurofibrillary tangles (NFT), ensuring the neuronal cell death in hippocampus region; a hallmark of Alzheimer’s disease (AD). Thus, designing inhibitor towards nNOS may reduce the neuronal loss caused by nNOS. Hence nNOS has been one of the revitalizing targets for AD. In the present work, one energetically optimized structure-based pharmacophore (e-pharmacophore) was generated using nNOS co-crystal structure (4D1N) to map important pharmacophoric features of nNOS.. View More»
DOI:
10.4172/2161-1009.1000307