Validated quantitative structure-activity relationship analysis of a series of 2-aminothiazole based p56(Lck) inhibitors

Anal Chim Acta. 2009 Jan 5;631(1):29-39. doi: 10.1016/j.aca.2008.10.026. Epub 2008 Oct 21.

Abstract

In this study, the quantitative structure-activity relationship (QSAR) of a series of 2-aminothiazole based Lck inhibitors was investigated. The key structural features responsible for the inhibition activities were discussed in detail. A population of 100 rigorously validated linear QSAR models were established based on the descriptors calculated in DRAGON program and selected by genetic algorithm (GA). A total of 36 descriptors were involved in all the QSAR models. Then the common descriptors appeared in all the models were extracted to build the final QSAR model. As a result, the final 8-parameter QSAR model was established. After analysis of the eight descriptors, some advice was proposed to help the design of possible novel inhibitors with higher bioactivity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Artificial Intelligence
  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / pharmacology*
  • Genetics
  • Linear Models
  • Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / antagonists & inhibitors*
  • Quantitative Structure-Activity Relationship*
  • Reproducibility of Results
  • Thiazoles / chemistry*
  • Thiazoles / pharmacology*

Substances

  • Enzyme Inhibitors
  • Thiazoles
  • 2-aminothiazole
  • Lymphocyte Specific Protein Tyrosine Kinase p56(lck)