title: (+)-Arisugacin A--computational evidence of a dual binding site covalent inhibitor of acetylcholinesterase.
abstract: A computation docking study of the highly potent, non-nitrogen containing, acetylcholinesterase inhibitor (+)-arisugacin A is presented. The model suggests that (+)-arisugacin A is a dual binding site covalent inhibitor of AChE. These findings are examined in the context of Alzheimer's disease-modifying therapeutic design. (+)-Arisugacin A's revealed mode of action is unique, and may serve as a basis for the development of AD therapeutics capable of treating the symptomatic aspects of AD, while being neuroprotective with long term efficacy.
authors.affiliation: Alchemical Research, LLC, 426 Heckewelder Place, Bethlehem, PA 18018, USA. zalrashid@alchemicalresearch.com
authors.forename: Ziyad F
authors.initials: ZF
authors.lastname: Al-Rashid
authors.forename: Richard P
authors.initials: RP
authors.lastname: Hsung
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy; D001665:Binding Sites / Q000187:drug effects; D002800:Cholinesterase Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D003198:Computer Simulation; D020128:Inhibitory Concentration 50; D008954:Models, Biological; D008958:Models, Molecular; D015394:Molecular Structure; D011714:Pyrans / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D002800:Cholinesterase Inhibitors; D011714:Pyrans; C432303:arisugacin A