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: Miguel O Mitchell, Robert W Figliozzi, Mustafa Guzel
• Journal: Medicinal chemistry (Shariqah (United Arab Emirates)) (Med Chem) Vol. 6 Issue 3 Pg. 141-3 (May 2010) ISSN: 1875-6638 [Electronic] Netherlands
• PMID: 20632975 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Alkaloids
• Cholinesterase Inhibitors
• debromoflustramine B
• Butyrylcholinesterase

Topics

• Alkaloids (chemistry)
• Alzheimer Disease (enzymology)
• Animals
• Binding Sites
• Bryozoa (chemistry)
• Butyrylcholinesterase (metabolism)
• Cholinesterase Inhibitors (chemistry)
• Humans
• Inhibitory Concentration 50
• Molecular Dynamics Simulation
• Stereoisomerism
• Structure-Activity Relationship