Biochemistry (Moscow)

, Volume 80, Issue 1, pp 74–86

Quantitative analysis of structure-activity relationships of tetrahydro-2H-isoindole cyclooxygenase-2 inhibitors

Article

DOI: 10.1134/S0006297915010095

Cite this article as:
Khayrullina, V.R., Gerchikov, A.Y., Lagunin, A.A. et al. Biochemistry Moscow (2015) 80: 74. doi:10.1134/S0006297915010095

Abstract

Using the GUSAR program, structure-activity relationships on inhibition of cyclooxygenase-2 (COX-2) catalytic activity were quantitatively analyzed for twenty-six derivatives of 4,5,6,7-tetrahydro-2H-isoindole, 2,3-dihydro-1H-pyrrolyzine, and benzothiophene in the concentration range of 0.6–700 nmol/liter IC50 values. Six statistically significant consensus QSAR models for prediction of IC50 values were designed based on MNA- and QNA-descriptors and their combinations. These models demonstrated high accuracy in the prediction of IC50 values for structures of both training and test sets. Structural fragments of the COX-2 inhibitors capable of strengthening or weakening the desired property were determined using the same program. This information can be taken into consideration on molecular design of new COX-2 inhibitors. It was shown that in most cases, the influence of structural fragments on the inhibitory activity of the studied compounds revealed with the GUSAR program coincided with the results of expert evaluation of their effects based on known experimental data, and this can be used for optimization of structures to change the value of their biological activity.

Key words

cyclooxygenase-2 inhibitors GUSAR QSAR models QNA and MNA descriptors analysis of structure-activity relationships 

Abbreviations

COX-1(2)

cyclooxygenase-1(2)

GUSAR

General Unrestricted Structure-Activity Relationships

MNA

Multilevel Neighborhoods of Atoms

QSAR

Quantitative Structure-Activity Relationships

Copyright information

© Pleiades Publishing, Ltd. 2015

Authors and Affiliations

  1. 1.Faculty of ChemistryBashkir State UniversityUfaRussia
  2. 2.Medico-Biological FacultyPirogov Russian National Research Medical UniversityMoscowRussia
  3. 3.Orekhovich Institute of Biomedical ChemistryRussian Academy of Medical SciencesMoscowRussia
  4. 4.Bashkir State Medical UniversityUfaRussia

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