Journal of Computer-Aided Molecular Design

, Volume 16, Issue 11, pp 769–778 | Cite as

Binding models of reversible inhibitors to type-B monoamine oxidase

  • Antonio Carrieri
  • Andrea Carotti
  • M. Letizia Barreca
  • Cosimo Altomare

Abstract

Interest in the inhibitors of type-B monoamine oxidase has grown in recent years, due to the evidence for multiple roles of one such agent (selegiline) in the pharmacological management of neurodegenerative disorders. A set of 130 reversible and selective inhibitors of MAO-B (including tetrazole, oxadiazolone, and oxadiazinone derivatives) were taken from the literature and subjected to a three-dimensional quantitative structure–activity relationship (3D-QSAR) study, using CoMFA and GOLPE procedures. The steric and lipophilic fields, alone and in combination, provided us with informative models and satisfactory predictions (q2=0.73). The validity of these models was checked against the 3D X-ray structure of human MAO-B. Flexible docking calculations, performed by using a new approach which took advantage from QXP and GRID computational tools, showed the diverse inhibitors to interact with MAO-B in a similar binding mode, irrespective of the heterocycle characterizing them. A significant trend of correlation was observed between estimated energies of the complexes and the experimental inhibition data.

Monoamine oxidase-B reversible MAO-B inhibitors three-dimensional quantitative structure-activity relationships docking calculations 

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Copyright information

© Kluwer Academic Publishers 2002

Authors and Affiliations

  • Antonio Carrieri
    • 1
  • Andrea Carotti
    • 1
  • M. Letizia Barreca
    • 2
  • Cosimo Altomare
    • 1
  1. 1.Dipartimento Farmaco-ChimicoUniversità di BariBariItaly
  2. 2.Dipartimento Farmaco-ChimicoUniversità di MessinaMessinaItaly

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