SYNTHESIS AND EVALUATION OF ANTIMICROBIAL ACTIVITY OF NEW 1,3,5-TRIAZINE DERIVATIVES

DOI: https://doi.org/10.29296/25877313-2022-07-06
Issue: 
7
Year: 
2022

E.V. Kuvaeva
Ph.D. (Pharm.), Аssociate Professor, Department of Organic Chemistry,
Saint-Petersburg State Chemical and Pharmaceutical University (Saint-Petersburg, Russia)
E-mail: elena.kuvaeva@pharminnotech.com
P.O. Levshukova
Student,
Saint-Petersburg State Chemical and Pharmaceutical University (Saint-Petersburg, Russia)
Е-mail: levshukova.polina@pharminnotech.com
D.A. Kolesnik
Ph.D. (Pharm.), Assistant, Department of Organic Chemistry,
Saint-Petersburg State Chemical and Pharmaceutical University (Saint-Petersburg, Russia)
Е-mail: denis.kolesnik@spcpu.ru
E.N. Kirillova
Ph.D. (Chem.), Associate Professor, Department of Organic Chemistry,
Saint-Petersburg State Chemical and Pharmaceutical University (Saint-Petersburg, Russia)
E-mail: eugenia.kirillova@pharminnotech.com
I.P. Yakovlev
Dr.Sc. (Chem.), Рrofessor, Head of the Department of Organic Chemistry,
Saint-Petersburg State Chemical and Pharmaceutical University (Saint-Petersburg, Russia)
E-mail: igor.yakovlev@pharminnotech.com
Yu.M. Ladutko
Ph.D. (Pharm.), Аssociate Professor, Department of Medicinal Forms Technology,
Saint-Petersburg State Chemical and Pharmaceutical University, (Saint-Petersburg, Russia)
E-mail: yulia.ladutko@pharminnotech.com

Aim. Synthesis of new 1,3,5-triazine derivatives (studied compounds, target compounds) and evaluation of their antimicrobial activity in silico and in vitro. Material and methods. The target compounds were obtained as a result of the reaction of 2,5-disubstituted-4-hydroxy-6H-1,3-oxazin-6-ones and S-methylisothiourea hemisulfate in the presence of an equimolar amount of sodium methylate in a methanol medium. The structure has been proven using modern physico-chemical analysis methods. Computer screening of biological activity was carried out using the PASS program located on the web service and accessible via the Internet. Experimentally, the antimicrobial activity of the compounds was studied in relation to the test culture of the microorganism – Staphylococcus aureus P209. Results. New derivatives of 1,3,5-triazine were synthesized with a yield of 66–72%. The structure of the obtained compounds was proved using 1H and 13C NMR spectroscopy, IR spectroscopy. As a result of screening of biological activity using the PASS program, data on a pronounced antimicrobial effect were obtained. The study of antimicrobial activity in vitro showed that the target compounds have an effect on Staphylococcus aureus P209. Conclusion. New derivatives of 1,3,5-triazine – 2-(methylthio)-4-(4-nitrophenyl)-6-ethyl-1,3,5-triazine, 2-(methylthio)-4-phenyl-6-ethyl-1,3,5-triazine, 2-(methylthio)-4-(4-methylphenyl) were synthesized-6-ethyl-1,3,5-triazine. Their structure has been proved using modern physico-chemical analysis methods. The results of computer prediction made it possible to determine the potential biological activity. Experimental microbiological studies have proved that the studied compounds have antimicrobial activity against Staphylococcus aureus P209.

Keywords: 
1 3 5-triazines
antimicrobial activity
computer screening
Staphylococcus aureus
4-hydroxy-6H-1 3-oxazin-6-ones
Staphylococcus aureus
4-hydroxy-6H-1
3-oxazin-6-ones

References: 
  1. Patel R.V., Kumari P., Rajani D.P., Chikhalia K.H. Synthesis, characterization and pharmacological activities of 2-[4-cyano-(3-trifluoromethyl)phenyl amino)]-4-(4-quinoline/coumarin-4-yloxy)-6-(fluoropiperazinyl)-s-triazines. Journal of Fluorine Chemistry. 2011; 132: 617–627.
  2. Shah D.R., Modh R.P., Chikhalia K.H. Privileged s-triazines: structure and pharmacological applications. Future Med. Chem. 2014; 6(4): 463–477. DOI: 10.4155/fmc.13.212.
  3. McKay G.A., Reddy R., Arhin F., Belley A., Lehoux D., Moeck G., Sarmiento I., Parr T.R., Gros P., Pelletier J., Far A.R. 3-(Indol-2-yl)indazoles as Chek1 kinase inhibi-tors: Optimization of potency and selectivity via substitution at C6. Bioorganic & Medicinal Chemistry Letters. 2006; 16: 1286.
  4. Baldaniya B.B., Patel P.K. Synthesis, Antibacterial and Antifungal Activities of s-Triazine Derivatives. Eur. Journal of Chemistry. 2009; 6(3): 673.
  5. PASS Online. Way2Drug: [veb-resurs]. Moskva. URL: www.way2drug.com/PASSOnline (data obrashcheniya 24.01.2021). Rezhim dostupa: dlya zaregistrir. pol'zovatelej. Tekst: elektronnyj.
  6. Gosudarstvennaya farmakopeya Rossijskoj Federacii. MZ RF. XIV izd. T.3. Moskva, 2018; 1187 s.
  7. Mironov A.N. Rukovodstvo po provedeniyu doklinicheskih issledovanij lekarstvennyh sredstv. Chast' pervaya. M.: Grif i K. 2012; 944 s.
  8. Patent 2765005 S1. Sposob polucheniya 2-(metiltio)-4-(4-nitrofenil)-6-etil-1,3,5-triazina / D.A. Kolesnik, E.V. Kuvaeva, T.L. Semakova, O.Yu. Strelova, I.P. Yakovlev, G.V. Ksenofontova; zayavitel' i patentoobladatel' FGBOU VO SPHFU Minzdrava Rossii. № 2020139481; zayavl. 30.11.2020; opubl. 24.01.2022.