Structure–activity relationship and docking studies of thiazolidinedione-type compounds with monoamine oxidase B

• Published in: Bioorganic & medicinal chemistry letters Vol. 21; no. 16; pp. 4798 - 4803
• Main Authors: Carroll, Richard T., Dluzen, Dean E., Stinnett, Hilary, Awale, Prabha S., Funk, Max O., Geldenhuys, Werner J.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Ltd 15.08.2011; Elsevier
• Subjects: Amplex-Red; Animals; Anticonvulsants. Antiepileptics. Antiparkinson agents; Biological and medical sciences; Enzyme; Humans; Kynuramine; Male; Medical sciences; Mice; Mice, Inbred C57BL; Models, Molecular; Molecular Structure; Monoamine Oxidase - metabolism; Monoamine Oxidase Inhibitors - chemical synthesis; Monoamine Oxidase Inhibitors - chemistry; Monoamine Oxidase Inhibitors - pharmacology; MPTP; Neuropharmacology; Pharmacology. Drug treatments; Pharmacophore; Stereoisomerism; Structure-Activity Relationship; Thiazolidinediones - chemical synthesis; Thiazolidinediones - chemistry; Thiazolidinediones - pharmacology; Amplex-Red; MPTP; Enzyme; Pharmacophore; Kynuramine; Five membered ring; Monoamine oxidase B inhibitor; Isozyme; Parkinson disease; Modeling; Structure activity relation; Molecular model; Binding mode; Degenerative disease; Sulfur nitrogen heterocycle; Nervous system diseases; Rodentia; Benzene derivatives; Enzyme inhibitor; Inhibitor enzyme complex; Neuroprotective agent; Antiparkinson agent; In vitro; Amine oxidase (flavin-containing); Cerebral disorder; In vivo; Vertebrata; Chemotherapy; Mammalia; Treatment; Mouse; Animal; Central nervous system disease; Phenols; Oxidoreductases; Extrapyramidal syndrome
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2011.06.060

NL-1 (1) docks with the aromatic moiety in the substrate cavity of human MAO-B. The neuroprotective activity of pioglitazone and rosiglitazone in the MPTP parkinsonian mouse prompted us to evaluate a set of thiazolidinedione (TZD) type compounds for monoamine oxidase A and B inhibition activity. These compounds were able to inhibit MAO-B over several log units of magnitude (82nM to 600μM). Initial structure–activity relationship studies identified key areas to modify the aromatic substituted TZD compounds. Primarily, substitutions on the aromatic group and the TZD nitrogen were key areas where activity was enhanced within this group of compounds.