Synthesis and evaluation of aplysinopsin analogs as inhibitors of human monoamine oxidase A and B.

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Lewellyn K, Bialonska D, Chaurasiya ND, Tekwani BL, Zjawiony JK

Synthesis and evaluation of aplysinopsin analogs as inhibitors of human monoamine oxidase A and B.

Bioorg Med Chem Lett. 2012 Aug 1;22(15):4926-9. doi: 10.1016/j.bmcl.2012.06.058. Epub 2012 Jun 23.

PubMed ID

22781190 [ View in PubMed

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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.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Clorgiline	Amine oxidase [flavin-containing] A	IC 50 (nM)	6.7	N/A	N/A	Details
Selegiline	Amine oxidase [flavin-containing] B	IC 50 (nM)	45	N/A	N/A	Details