title: In silico ligand-receptor docking of potentially selective butyrylcholinesterase inhibitors structurally related to the marine natural product debromoflustramine B.
abstract: Selective human butyrylcholinesterase (BChE) inhibitors such as cymserine have shown considerable promise for restoring cognition in Alzheimer's disease. Recently, (-)-debromoflustramine B, 1, a hexahydropyrrolo-[2,3-b]indole natural product isolated from the marine bryozoan Flustra foliacea, has demonstrated micromolar potency as a selective BChE inhibitor. Since (±)-demethyldebromoflustramine B, (±)-2, has an even lower IC(50), and the active enantiomer is (-)-2, derivatives of (-)-2 were constructed in silico and docked into the active site of BChE. Several compounds exhibited improved inhibitor potency and could be candidates for future synthesis and in vitro enzyme inhibition study.
authors.affiliation: Department of Chemistry, Henson School of Science and Technology, Salisbury University, Salisbury, MD 21801, USA. momitchell@salisbury. edu
authors.forename: Miguel O
authors.initials: MO
authors.lastname: Mitchell
authors.forename: Robert W
authors.initials: RW
authors.lastname: Figliozzi
authors.forename: Mustafa
authors.initials: M
authors.lastname: Guzel
mesh_terms: D000470:Alkaloids / Q000737:chemistry*; D000544:Alzheimer Disease / Q000201:enzymology; D000818:Animals; D001665:Binding Sites; D002013:Bryozoa / Q000737:chemistry; D002091:Butyrylcholinesterase / Q000378:metabolism*; D002800:Cholinesterase Inhibitors / Q000737:chemistry*; D006801:Humans; D020128:Inhibitory Concentration 50; D056004:Molecular Dynamics Simulation; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D000470:Alkaloids; D002800:Cholinesterase Inhibitors; C090331:debromoflustramine B; D002091:Butyrylcholinesterase