3D Pharmacophore modeling in the molecules of 5,7-dimethyl-6-phenylazo-3H-thiazolo[4,5-b]pyridine-2-one derivatives

Authors

  • O. V. Klenina Lviv National Medical University named after Danylo Halytsky, Ukraine
  • T. I. Chaban Lviv National Medical University named after Danylo Halytsky, Ukraine
  • V. V. Ogurtsov Lviv National Medical University named after Danylo Halytsky, Ukraine
  • I. G. Chaban Lviv National Medical University named after Danylo Halytsky, Ukraine
  • I. Ya. Golos Lviv National Medical University named after Danylo Halytsky, Ukraine

DOI:

https://doi.org/10.24959/ophcj.14.768

Keywords:

thiazolo[4, 5-b]pyridines, pharmacophores, virtual screening, docking, protein-ligand interaction fingerprints

Abstract

Flexible molecular docking studies for 5,7-dimethyl-6-phenylazo-3H-thiazolo[4,5-b]pyridin-2-ones have been performed with the purpose to reveal their potency as enzymes involved in the arachidonic acid (AA) cascade inhibitors: both cyclooxygenase isoforms (COX-1 and COX-2), and microsomal prostaglandin E synthase-1 (mPGES-1). The protein-ligand interaction fingerprint (PLIF) tool implemented in MOE software has been used for summarizing the interactions between ligands and the abovementioned enzymes. Receptor interaction fingerprints have been generated from the docked poses of the virtual screening hits with COX-1,2 and mPGES-1 active sites coordinates. 3D pharmacophore models containing two and three points queries as the combination of their structures steric and electronic parameters have been generated and it provides the affinity and inhibitory activity of the novel compounds towards multiply receptors. The analysis of the pharmacophore models obtained indicates the functionality of fused bicyclic thiazolopyridine scaffold which provides the steric placement of at least one of these heterocycles atoms in the respective pharmacophore centres. The fused thiazolo[4,5-b]pyridine-2-one system may be considered as a promosing scaffold for creating diverse combinatorial libraries of potential biologically active substances. The final conclusion has been confirmed by the results of the virtual screening procedures and pharmacophore centres modeling in molecules of novel thiazolo [4,5-b]pyridine-2-one.

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Published

2014-03-06

How to Cite

(1)
Klenina, O. V.; Chaban, T. I.; Ogurtsov, V. V.; Chaban, I. G.; Golos, I. Y. 3D Pharmacophore Modeling in the Molecules of 5,7-Dimethyl-6-Phenylazo-3H-thiazolo[4,5-b]pyridine-2-One Derivatives. J. Org. Pharm. Chem. 2014, 12, 60-68.

Issue

Vol. 12 No. 1(45) (2014)

Section

Original Researches

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