Synthesis, physical-chemical and biological properties of 7-benzyl-3-methyl-8-thioxanthine derivatives

Authors

  • D. H. Ivanchenko Zaporizhzhia State Medical University, Ukraine,
  • M. I. Romanenko Zaporizhzhia State Medical University, Ukraine,
  • O. M. Kamyshnyi Zaporizhzhia State Medical University, Ukraine,
  • N. M. Polishchuk Zaporizhzhia State Medical University, Ukraine,
  • K. V. Aleksandrova Zaporizhzhia State Medical University, Ukraine,

DOI:

https://doi.org/10.14739/2409-2932.2017.3.113253

Keywords:

xanthine, organic synthesis, NMR-spectroscopy, antibacterial, antifungal agents, antioxidant effect

Abstract

Introduction . Interest to the problem of creating new effective antimicrobial agents among xanthine derivatives does not decrease. Primarily, this is due to the increasing of microbial resistance to conventional antimicrobial agents and the emergence of their new strains. In recent years interest to the therapeutic use of antioxidants in the treatment of diseases associated with oxidative stress has increased.

The aim of this work is to elaborate simple laboratory methods of 7-benzyl-3-methyl-8-thioxanthine derivatives synthesis, unspecified in scientific papers earlier, and to study their physical, chemical and biological properties.

Materials and methods. The melting point has been determined with the help of an open capillary method with PTP-M device. Elemental analysis has been performed with the help of the instrument Elementar Vario L cube, NMR-spectra have been taken on a spectrometer Bruker SF-400 (operating frequency of 400 MHz, solvent DMSO, internal standard – TMS). Study of antimicrobial and antifungal activity of synthesized compounds has been performed by two-fold serial dilution method. Standard test strains have been used for the study: Escherichia coli ATCC 25922, Staphylococcus aureus ATCC 25923, Pseudomonas aeruginosa ATCC 27853, Candida albicans ATCC 885-653. Dimethylsulfoxide was used as the solvent of the compounds.

Results. Under short-time heating up of the initial 7-benzyl-3-methyl-8-thioxanthine with alkyl, alkenyl, benzyl halides or heteroalkylchlorides in a water-propanol-2 mixture in the presence of an equimolar amount of sodium hydroxide leads to the formation of 8-S-substituted of 7-benzyl-3-methylxanthines. Structure of synthesized compounds was definitely proved by NMR-spectroscopy. We conducted primary screening research of antimicrobial activity of 7-benzyl-3-methyl-8-thioxanthine derivatives, which revealed moderate and weak activity in concentrations 50-100 mcg/ml. Most of the obtained compounds showed a pronounced antifungal effect. It was established that synthesized substances have weak antioxidant activity.

Conclusions. Accessible laboratory methods have been elaborated for synthesis of 7-benzyl-3-methyl-8-thioxanthine derivatives. The NMR spectral characteristics of the synthesized compounds have been analyzed and interpreted. Antimicrobial, antifungal and antioxidant activities of the obtained compounds have been explored. Priorities for further research of biologically active compounds have been outlined.


References

Hayallah, A. M., Elgaher, W. A., Salem, O. I., & Alim, A. A. M. A. (2011). Design and synthesis of some new theophylline derivatives with bronchodilator and antibacterial activities. Arch. Pharm. Res., 34(1), 3–21. doi: 10.1007/s12272-011-0101-8.

Hayallah, A. M., Talhouni, A. A., & Alim, A. A. M. A. (2012). Design and synthesis of new 8-anilide theophylline derivatives as bronchodilators and antibacterial agents. Arch. Pharm. Res., 35(8), 1355–1368. doi: 10.1007/s12272-012-0805-4.

Aleksandrova, K. V., Mykhalchenko, Ye. K., & Levich, S. V. (2017). Vyvchennia protymikrobnyh ta protyhrybkovykh vlastyvostei 7-zamishchenykh 3-benzyl-8-propilksantyniv [The study of antimicrobial and antifungal properties of 7- substituted of 3-benzyl-8-propylxanthine]. Medychnyi forum, 10(10), 9–12. [in Ukrainian].

Yoshikawa, T., & Naito, Y. (2002), What is oxidative stress? Japan Medical Association J., 45(7), 271–276.

Nikam, S., Nikam, P., Ahaley, S., & Sontakke, A. (2009) Oxidative stress in Parkinson’s disease. Indian J. of Clinical Biochemistry, 24(1), 98–101.

Carocho, M., & Ferreira, I. C.F.R. (2013), A review on antioxidants, prooxidants and related controversy: Natural and synthetic compounds, screening and analysis methodologies and future perspectives. Food and Chemical Toxicology, 51, 15–25. doi: 10.1016/j.fct.2012.09.021.

Romanenko, N. I., Fedulova, I. V., Ponomarenko, N. I., Gnatov, N. I., Klyuev, N. A., Priymenko, B. A., et al. (1989). Sintez 7-alkil-8-tioksantinov [Synthesis of 7-alkyl-8-thioxanthines]. Ukr. Chem. J., 55(6), 650–653. [in Russian].

Volianskyi, Yu. L., Hrytsenko, I. S., Shyrobokov, V. P., Smirnov, V. V., Biriukova, S. V., Dykyi, I. L., et al. (2004). Vyvchennia spetsyfichnoi aktyvnosti protymikrobnykh likarskykh zasobiv [The study of the specific activity of antimicrobial medicines: method. recommendations]. Kyiv [in Ukrainian].

Molyneux, Ph. (2004). The use of the stable free radical diphenylpicrylhydrazyl (DPPH) for estimating antioxidant activity. Songklanakarin J. Sci. Technol., 26(2), 212–219.

Al-Omair, M. A., Sayed, A. R., & Youssef, M. M. (2015). Synthesis of novel triazoles, tetrazine, thiadiazoles and their biological activities. Molecules, 20(2), 2591–2610. doi: 10.3390/molecules20022591.

How to Cite

1.
Ivanchenko DH, Romanenko MI, Kamyshnyi OM, Polishchuk NM, Aleksandrova KV. Synthesis, physical-chemical and biological properties of 7-benzyl-3-methyl-8-thioxanthine derivatives. Current issues in pharmacy and medicine: science and practice [Internet]. 2017Nov.1 [cited 2024May24];(3). Available from: http://pharmed.zsmu.edu.ua/article/view/113253

Issue

Section

Synthesis of the biologically active compounds