Synthesis and evaluation of aplysinopsin analogs as inhibitors of human monoamine oxidase A and B.
Bioorg Med Chem Lett, 2012/8/01;22(15):4926-9.
Lewellyn K[1], Bialonska D, Chaurasiya ND, Tekwani BL, Zjawiony JK
Affiliations
PMID: 22781190DOI: 10.1016/j.bmcl.2012.06.058
Impact factor: 2.94
Abstract
Aplysinopsins are tryptophan-derived natural products that have been isolated from a variety of marine organisms. Previous studies have shown aplysinopsin analogs to possess a variety of biological activities, including modulation of neurotransmissions. A series of fifty aplysinopsin analogs was synthesized and assayed for monoamine oxidase A and B inhibitory activity. Three compounds displayed significant MAO inhibitory activity and selectivity. The compound (E)-5-[(6-bromo-1H-indol-3-yl)methylene]-2-imino-1,3-dimethylimidazolidin-4-one (3x) possessed an IC(50) of 5.6 nM at MAO-A and had a selectivity index of 80.24. An SAR study revealed that multiple N-methylations, one of which should be at position N-2', and bromination at C-5 or C-6 are important factors for MAO-A potency and selectivity.
MeSH terms
Enzyme Activation; Enzyme Inhibitors; Humans; Monoamine Oxidase; Monoamine Oxidase Inhibitors; Protein Binding; Structure-Activity Relationship; Tryptophan
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