IN-SILICO IDENTIFICATION OF 6-HYDROXY-L-NICOTINE AS A NOVEL NEUROPROTECTIVE DRUG

Marius Mihăşan, Capatina Luminita, Elena Neagu, Marius Stefan, Lucian Hritcu, Marius Stefan, Alexandru
2013 Romanian Biotechnological Letters   unpublished
The implication of nicotinic acetylcholine receptors (nAChR) in Alzheimer's disease pathogenesis has led to the proposal of a new approach in AD therapeutic strategies. By using nAchR modulators to increase the availability of receptors for acetylcholine, the loss of forebrain cholinergic neurons can be overcome and the cognitive functions can be improved. In this direction, due to its affinity to nAChR, nicotine provides a strong scaffold for developing AD drugs. Using a set of in-silico
more » ... of in-silico tools, all the A. nicotinovoras pAOl metabolic intermediates from nicotine to the end-product nicotine-blue (NB) have been tested for their ability to bind nAChR. The round of computational localized docking experiments using the AchBP structure (PDB ID lUW6) as receptor indicated that the best ligand is 6-hydroxi-L-nicotine, with theoretical binding energy of-6.66 (-6.17 for nicotine). Moreover, 6HNic also has improved antioxidant properties, which also might increase its potential as neuroprotective drug with applications in Alzheimer's disease therapy.
fatcat:n37iroakzncifjpliytoxrqnsi