Development of selective and reversible pyrazoline based MAO-B inhibitors: virtual screening, synthesis and biological evaluation

Nibha Mishra; D Sasmal

doi:10.1016/j.bmcl.2011.02.030

Development of selective and reversible pyrazoline based MAO-B inhibitors: virtual screening, synthesis and biological evaluation

Bioorg Med Chem Lett. 2011 Apr 1;21(7):1969-73. doi: 10.1016/j.bmcl.2011.02.030. Epub 2011 Feb 13.

Authors

Nibha Mishra¹, D Sasmal

Affiliation

¹ Department of Pharmaceutical Sciences, Birla Institute of Technology, Mesra, Ranchi 835 215, India. nmishra@bitmesra.ac.in

PMID: 21377879
DOI: 10.1016/j.bmcl.2011.02.030

Abstract

In an effort to develop selective MAO (monoamine oxidase) B inhibitors, structure based virtual screening was initiated on an in-house library. Top 10 HITS were synthesized and evaluated for MAO (A and B) inhibitory activity, both against human and rat enzymes. All the compounds were found selective, reversible and active in nM range (100 times more potent than selegeline) towards MAO-B. Outstanding co-relation between predicted and experimental K(i) values were observed.

Publication types

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

MeSH terms

Animals
Combinatorial Chemistry Techniques
Drug Evaluation, Preclinical
Humans
Models, Molecular
Monoamine Oxidase / drug effects*
Monoamine Oxidase Inhibitors / chemical synthesis
Monoamine Oxidase Inhibitors / chemistry
Monoamine Oxidase Inhibitors / pharmacology*
Pyrazoles / chemical synthesis
Pyrazoles / chemistry
Pyrazoles / pharmacology*
Rats

Substances

Monoamine Oxidase Inhibitors
Pyrazoles
Monoamine Oxidase