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

Richard T Carroll; Dean E Dluzen; Hilary Stinnett; Prabha S Awale; Max O Funk; Werner J Geldenhuys

doi:10.1016/j.bmcl.2011.06.060

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

Bioorg Med Chem Lett. 2011 Aug 15;21(16):4798-803. doi: 10.1016/j.bmcl.2011.06.060. Epub 2011 Jun 21.

Authors

Richard T Carroll¹, Dean E Dluzen, Hilary Stinnett, Prabha S Awale, Max O Funk, Werner J Geldenhuys

Affiliation

¹ Department of Pharmaceutical Sciences, Northeastern Ohio Universities Colleges of Medicine and Pharmacy, 4209 State Route 44, Rootstown, OH 44272, USA.

PMID: 21742494
DOI: 10.1016/j.bmcl.2011.06.060

Abstract

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 (82 nM to 600 μM). 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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Humans
Male
Mice
Mice, Inbred C57BL
Models, Molecular
Molecular Structure
Monoamine Oxidase / metabolism*
Monoamine Oxidase Inhibitors / chemical synthesis
Monoamine Oxidase Inhibitors / chemistry
Monoamine Oxidase Inhibitors / pharmacology*
Stereoisomerism
Structure-Activity Relationship
Thiazolidinediones / chemical synthesis
Thiazolidinediones / chemistry
Thiazolidinediones / pharmacology*

Substances

Monoamine Oxidase Inhibitors
Thiazolidinediones
2,4-thiazolidinedione
Monoamine Oxidase