Purposeful search and characteristic of anti-inflammatory activity of sodium (3-R-2-оxo-2Н-[1,2,4]triazino[2,3-c]quinazolin-6-yl)alkylcarboxylates and their halogen containing analogues

Authors

  • V. V. Yakubovska Vinnytsya National Pirogov memorial Medical University,
  • N. М. Seredinska Instute Pharmacology and Toxicology NAMS Ukraine,
  • О. Yu. Voskoboynik Zaporizhzhia State Medical University,
  • G. І. Stepanyuk Vinnytsya National Pirogov memorial Medical University,
  • S. І. Kovalenko Zaporizhzhia State Medical University,

DOI:

https://doi.org/10.14739/2409-2932.2016.1.62036

Keywords:

sodium (3-R-2-oxo-2Н-[1, 2, 4]triazino[2, 3-c]quinazolin-6-il)carboxylates, halogen-containing analogues, molecular docking, anti-inflammatory activity

Abstract

Aim. The approaches for creating  novel agents with anti-inflammatory activity among sodium (3-R-2-oxo-2Н-[1,2,4]triazino[2,3-c]quinazolin-6-yl)alkylcarboxylates and their halogen containing analogues were described in presented article.

Methods and results. Mentioned methods have been based on combination of «in silico» screening with experimental studies. Affinity of studied compounds to the active center of COX-1 and COX-2 enzymes has been shown. Conducted visualization of compound – active site complex allowed to suppose the presence of anti-inflammatory activity of studied compounds.

Conclusions. It was established, that sodium (3-R-2-oxo-2Н-[1,2,4]triazino[2,3-c]quinazoline-6-yl)alkylcarboxylates and their halogen-containing analogues reveal anti-inflammatory activity, the most active was compound DSK-38 (ED50 – 4 mg/kg as against 8 mg/kg of diclofenac sodium). «Structure–activity» relationships features among studied compounds have been discussed.

References

Mashkovskij, M. D. (2008) Lekarstvennye sredstva [Drugs]. Moscow: RIA Novaya volna. [in Russian].

Stepaniuk, H. I., Chornoivan, N. H., Kovalenko, S. I., et al. (2011) Skryninh analhetychnoi aktyvnosti v riadu pokhidnykh(3-R-2-okso-2N-[1,2,4]tryazyno[2,3-c]khinazolin-6-il)karbonovykh kyslot [Screening of actoprotective activity among (3-R-2oxo-2N-[1,2,4]triazino[2,3-c]quinazoline-6-yl)carboxylic acids.]. Farmakolohіia ta lіkarska toksykolohіia, 1(20), 52–55. [in Ukrainian].

Semenenko, N. O. (2014) Tserebroprotektorni vlastyvosti pokhidnykh (3-R-2-okso-2N-[1,2,4]¬tryazyno[2,3-c]khinazolin-6-il)karbonovykh kyslot (Avtoref. dis…kand. med. nauk) [Cerebroprotective properties of (3-R-2-oxo-2H-[1,2,4]triazino[2,3-c]quinazolin-6-yl)carboxylic acid]. (Extended abstract of candidate’s thesis). Odesa. [in Ukrainian].

Stepaniuk, H. I., Pochelova, O. V., Stepaniuk, N. H., Kovalenko, S. І., & Voskoboinik, O. Yu. (2014) Aktoprotektorna aktyvnist solei (3-R-2-okso-2N-[1,2,4]-tryazyno[2,3-c]khinazolin-6-il)karbonovykh kyslot ta yikh halohenovmisnykh analohiv [Actoprotective activity of (3-R-2-oxo-2H-[1,2,4]-triazino[2,3-c]quinazolin-6-yl)carboxylic acids and their halogen-containing analogs]. Farmakolohiia ta likarska toksykolohiia, 4–5(40), 90–95. [in Ukrainian].

Chornoіvan, N. І., Voskoboinіk, O. Yu., Skorina, D. Yu., & Kovalenko, C.І. (patentee) (2013) Patent Ukrainy na korysnu model №81634 MPK (2013.01) A61K 31/00. Soli (3-R-8-R1-9-R2-10-R3-11-R4-2-okso-2N-[1,2,4]triazyno[2,3-s]khinazolin-6-il)alkilkarbonovykh kyslot, shcho pidvyshchuiut fizychnu vytryvalist orhanizmu [Patent of Ukraine for useful model № 81634 MPK (2013.01) A61K 31/00. Salts of (3-R-8-R1-9-R2-10-R3-11-R4-2-oxo-2H-[1,2,4]trіazino[2,3-c]quinazolin-6-yl)alkylcarboxilic acids, which increases the physical endurance of organism]. Biuleten, 13. [in Ukrainian].

Semenenko, N. O., Stepaniuk, H. І., Semenenko, A. І., Kovalenko, C. І., Voskoboinіk, O. Yu., & Skorina, D. Yu. (patentee) (2013) Patent Ukrainy na korysnu model №84257 MPK (2013.01) A61K 31/215. Zastosuvannia natriievoi soli 4-(2-okso-3-metyl-2N-[1,2,4]triazyno[2,3-s]khinazolin-6-il)-butanovoi kysloty v yakosti tserebroprotektornoho zasobu [Patent of Ukraine for useful model № 84257 MPK (2013.01) A61K 31/215. Usage of sodium salts of 4-(2-oxo-3-methyl-2H-[1,2,4]trіazino[2,3-c]quinazolin-6-yl)butanoic acids as cerebroprotective activity]. Biuleten, 19. [in Ukrainian].

Protein Data Bank, pdb. Retrieved from http://www.pdb.org

MarvinSketch version: 6.3.0, 2015; ChemAxon. Retrieved from http://www.chemaxon.com.

Trott, O., & Olson, A. J. (2010) AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization and multithreading. J. Comput. Chem., 31, 455–461. doi: 10.1002/jcc.21334.

Discovery Studio Visualizer v4.0.100.13345. Accelrys Software Inc.

Michael, F. (1999) Sanner. Python: A programming Language for Software Integration and Development. J. Mol. Graphics Mod., 17, 57–61.

Kozhemiakіn, I. M., Khromov, O. S., Fіlonenko, M. A., et al. (2002) Naukovo-metodychni rekomendatsii z utrymannia laboratornykh tvaryn ta roboty z nymy [Guidelines for care and working with laboratory animals]. Kyiv: Avіcena. [in Ukrainian].

Zapadnyuk, I. P., Zapadnyuk, V. I., Zakhariya, E. A., et al. (1983) Laboratornye zhivotnye. Razvedenie, soderzhanie, ispol`zovanie v e`ksperimente [Laboratory animals: breeding, care and usage in experiment]. Kyiv. [in Ukrainian].

(2009) Nakaz Ministerstva okhorony zdorov’ia Ukrainy «Poriadok provedennia doklinichnoho vyvchennia likarskykh zasobiv ta ekspertyzy materialiv doklinichnoho vyvchennia likarskykh zasobiv» ot 14.12.2009 r. №944 [Ministry of public health of Ukraine order «Rules for conduction of preclinical study of drugs and expertise of materials of preclinical study of drugs» 14 December 2009 №944]. [in Ukrainian].

(1986). European convention for the protection of vertebrate animal used for experimental and other scientific purposes. – Council of Europe, Strasbourg.

Stepanyuk, G. I. (1989) Protivovospalitel'nye, anal'geticheskie i vazoaktivnye svojstva proizvodnykh benzofurana (Avtoref. dis… dokt. med. nauk) [Anti-inflammatory, analgesic and vasoactive properties of benzofurane derivatives]. Dr. med. sci. diss.]. Kyiv. [in Ukrainian].

Drohovoz, S. M., Zupanets, I. A., Mokhort, M. A., Yakovleva, L. V., & Klebanov, B. M. (2001) Eksperymentalne (doklinichne) vyvchennia farmakolohichnykh rechovyn, yaki proponuiutsia yak nesteroidni protyzapalni zasoby [Experimental (preclinical) study of potential non-steroid anti-inflammatory drugs]. Doklinichni doslidzhennia likarskykh zasobiv, O.V. Stefanov (Ed). (S. 292–306). Kyiv: Avіcenna. [in Ukrainian].

Rebrova, O. Yu. (2006) Statisticheskij analiz medicinskikh dannykh. Primenenie paketa prikladnykh program Statistica [Statistical analysis of medicinal data using Statistica software]. Мoscow: MediaSfera. [in Russian].

Downloads

How to Cite

1.
Yakubovska VV, Seredinska NМ, Voskoboynik ОY, Stepanyuk GІ, Kovalenko SІ. Purposeful search and characteristic of anti-inflammatory activity of sodium (3-R-2-оxo-2Н-[1,2,4]triazino[2,3-c]quinazolin-6-yl)alkylcarboxylates and their halogen containing analogues. Current issues in pharmacy and medicine: science and practice [Internet]. 2016Mar.9 [cited 2024Apr.23];(1). Available from: http://pharmed.zsmu.edu.ua/article/view/62036

Issue

No. 1 (2016)

Section

Experimental and clinical pharmacology

License

Authors who publish with this journal agree to the following terms:

    1. Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.     Лицензия Creative Commons
    2. Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
    3. Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access)