Publication Abstract from PubMed
Monoamine oxidases (MAO) and cholinesterases are validated targets in the design of drugs for the treatment of Alzheimer's disease. The multi-target compound N-((5-(3-(1-benzylpiperidin-4-yl)propoxy)-1-methyl-1H-indol-2-yl)methyl)-N-methyl prop-2-yn-1-amine (ASS234), bearing the MAO-inhibiting propargyl group attached to a donepezil moiety that inhibits cholinesterases, retained activity against human acetyl- and butyryl-cholinesterases. The inhibition of MAO A and MAO B by ASS234 was characterized and compared to other known MAO inhibitors. ASS234 was almost as effective as clorgyline (kinact/KI=3x106 min-1M-1) and was shown by structural studies to form the same N5 covalent adduct with the FAD cofactor.
Kinetic and structural analysis of the irreversible inhibition of human monoamine oxidases by ASS234, a multi-target compound designed for use in Alzheimer's disease.,Esteban G, Allan J, Samadi A, Mattevi A, Unzeta M, Marco-Contelles J, Binda C, Ramsay RR Biochim Biophys Acta. 2014 Mar 16. pii: S1570-9639(14)00056-9. doi:, 10.1016/j.bbapap.2014.03.006. PMID:24642166[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
