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QSAR and pharmacophore models for screening antiinflammatory activity among substituted (pyrrolо[1,2- a][1,2,4]triazino[2,3-c]quinazoline-5a-yl)carboxylic acids

Year 2022, Volume: 26 Issue: 5, 1420 - 1431, 28.06.2025

Viktor Stavytskyi Oleksii Voskoboinik , Oleg Devinyak Oleksii Voskoboinik , Sergiy Kovalenko

Abstract

This study is devoted to the development of QSAR and pharmacophore models for screening of antiinflammatory
activity among substituted (pyrrolo[1,2-a][1,2,4]triazino[2,3-c]quinazoline-5a-yl)carboxylic acids,
obtained in earlier research of our scientist group. Genetic algorithm–multiple linear regression allowed to calculate
two three-parameter QSAR equations for each model of experimental inflammation. It was found that the antiinflammatory
activity in the "carrageenan" model depends on the descriptors GATS5m and B10[C-O] and the presence
in the structure nROH functional group. Whereas, in the "formalin" model, pharmacological effect is determined by the
descriptors E2p, R2e+, F09[N-F], that reveal positive contribution to the anti-inflammatory activity. The obtained
equations are characterized by significant predictive power and are determined by both internal and external validation.
The parameters of prognostic ability, namely the values of the cross-validation Q2LOO coefficient, are 0.8509 and 0.7653
respectively. Using pharmacophore modeling, it was found that substituted (pyrrolo[1,2-a][1,2,4]triazino[2,3-
c]quinazoline-5a-yl)carboxylic acids bind with potential biotargets through the carboxyl moiety at the 5a position
(potential participant in the formation of hydrogen bonds), regardless of the model of experimental inflammation.
Additional factors influencing activity are electron withdrawing substituents, namely aromatic (fluorophenyl) cycle at
the certain distance and oxygen at the second position in the molecule. The aforesaid shows the prospects for further
structural modification of the molecule by replacing the triazole ring with azole one or by removing it while retaining
the noted pharmacophore fragments. It is important that the developed models complement each other and can later
be used for virtual screening of anti-inflammatory activity among quinazolines and its condensed analogues.

Keywords

Pyrrolo[1-2-a][1-2-4]triazino[2-3-c]quinazolines anti-inflammatory activity QSAR- and pharmacophoric models screening

References

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There are 32 citations in total.

Details

Primary Language English
Subjects Pharmaceutical Sciences
Journal Section Articles
Authors

Viktor Stavytskyi 0000-0001-5897-5845

Oleksii Voskoboinik 0000-0002-8048-445X

Oleg Devinyak 0000-0001-5696-7614

Oleksii Voskoboinik 0000-0002-5790-3564

Sergiy Kovalenko 0000-0001-8017-9108

Publication Date June 28, 2025
Published in Issue Year 2022 Volume: 26 Issue: 5

Cite

APA Stavytskyi, V., Voskoboinik, O., Devinyak, O., Voskoboinik, O., et al. (2025). QSAR and pharmacophore models for screening antiinflammatory activity among substituted (pyrrolо[1,2- a][1,2,4]triazino[2,3-c]quinazoline-5a-yl)carboxylic acids. Journal of Research in Pharmacy, 26(5), 1420-1431.
AMA Stavytskyi V, Voskoboinik O, Devinyak O, Voskoboinik O, Kovalenko S. QSAR and pharmacophore models for screening antiinflammatory activity among substituted (pyrrolо[1,2- a][1,2,4]triazino[2,3-c]quinazoline-5a-yl)carboxylic acids. J. Res. Pharm. June 2025;26(5):1420-1431.
Chicago Stavytskyi, Viktor, Oleksii Voskoboinik, Oleg Devinyak, Oleksii Voskoboinik, and Sergiy Kovalenko. “QSAR and Pharmacophore Models for Screening Antiinflammatory Activity Among Substituted (pyrrolо[1,2- a][1,2,4]triazino[2,3-c]quinazoline-5a-yl)carboxylic Acids”. Journal of Research in Pharmacy 26, no. 5 (June 2025): 1420-31.
EndNote Stavytskyi V, Voskoboinik O, Devinyak O, Voskoboinik O, Kovalenko S (June 1, 2025) QSAR and pharmacophore models for screening antiinflammatory activity among substituted (pyrrolо[1,2- a][1,2,4]triazino[2,3-c]quinazoline-5a-yl)carboxylic acids. Journal of Research in Pharmacy 26 5 1420–1431.
IEEE V. Stavytskyi, O. Voskoboinik, O. Devinyak, O. Voskoboinik, and S. Kovalenko, “QSAR and pharmacophore models for screening antiinflammatory activity among substituted (pyrrolо[1,2- a][1,2,4]triazino[2,3-c]quinazoline-5a-yl)carboxylic acids”, J. Res. Pharm., vol. 26, no. 5, pp. 1420–1431, 2025.
ISNAD Stavytskyi, Viktor et al. “QSAR and Pharmacophore Models for Screening Antiinflammatory Activity Among Substituted (pyrrolо[1,2- a][1,2,4]triazino[2,3-c]quinazoline-5a-yl)carboxylic Acids”. Journal of Research in Pharmacy 26/5 (June 2025), 1420-1431.
JAMA Stavytskyi V, Voskoboinik O, Devinyak O, Voskoboinik O, Kovalenko S. QSAR and pharmacophore models for screening antiinflammatory activity among substituted (pyrrolо[1,2- a][1,2,4]triazino[2,3-c]quinazoline-5a-yl)carboxylic acids. J. Res. Pharm. 2025;26:1420–1431.
MLA Stavytskyi, Viktor et al. “QSAR and Pharmacophore Models for Screening Antiinflammatory Activity Among Substituted (pyrrolо[1,2- a][1,2,4]triazino[2,3-c]quinazoline-5a-yl)carboxylic Acids”. Journal of Research in Pharmacy, vol. 26, no. 5, 2025, pp. 1420-31.
Vancouver Stavytskyi V, Voskoboinik O, Devinyak O, Voskoboinik O, Kovalenko S. QSAR and pharmacophore models for screening antiinflammatory activity among substituted (pyrrolо[1,2- a][1,2,4]triazino[2,3-c]quinazoline-5a-yl)carboxylic acids. J. Res. Pharm. 2025;26(5):1420-31.