Synthesis, physical-chemical and biological properties of 8-aminoderivatives of 7-alkyl-3-methylxanthines

  • M. I. Romanenko Zaporizhzhia State Medical University
  • M. V. Nazarenko Zaporizhzhia State Medical University
  • D. G. Ivanchenko Zaporizhzhia State Medical University
  • O. M. Kamyshny Zaporizhzhia State Medical University
  • N. M. Polishchuk Zaporizhzhia State Medical University
Keywords: synthesis, 3-methylxanthine, 8-aminoderivatives, NMR-spectroscopy, antimicrobial activity

Abstract

The search for new high-performance antimicrobial compounds remains one of the most important tasks of modern pharmaceutical chemistry, despite the wide range of modern natural, synthetic and semi-synthetic drugs for the treatment of infectious diseases.This is especially true for the naturally occurring compounds, new non-toxic and effective drugs can be created by their chemical modification for the treatment of various infectious pathologies. Recent researches in this area point to significant prospect of new synthetic derivatives of xanthine.

The aim of this work is to develop simple laboratory methods for synthesizing 8-aminoderivatives of 7-alkyl-3-methylxanthines and to study their physical and chemical peculiarities and antimicrobial properties.

The meltingpoint has been determined with the help of an open capillary method with TAP device (M). Elemental analysis has been performed with the help of the instrument ElementarVario L cube, NMR-spectra have been taken on a spectrometer Bruker SF-400 (operating frequency of 400 MHz, solvent DMSO-d6, internal standard – TMS). These data correspond to the calculated elemental analysis.

For the initial screening study of the newly-synthesized substances benchmark testing-cultures of both gram-positive and gram-negative bacteria have been used, which belong to clinically significant groups of infections agents which are differing by their morpho-physiological properties.

Through the reaction of 7-alkyl-3-methylxanthines with primary and secondary amines in water, water-ethanol, water-dioxane or cellosolve environment a range of 8-aminoderivativeshas been obtained which was not described earlier.

Developing accessible laboratory methods to synthesize new 8-aminoderivatives of 7-alkyl-3-methylxanthines, which are potential bioactive compounds. Studying NMR-spectral characteristics of the obtained substances.

Initial screening research of antimicrobial activity of the synthesized compounds has shown that 8-aminoxanthines (4, 6–12) can be used in medical practice as antistaphylococcal drugs, and 3-methyl-8-(4-methylpiperidine-1-yl)-7-n-propilxanthine (5)– antifungal agentafter additional studies.

References

1. Mashkovsky M. D. Medicines. Izd. 16th, transfiguration, correction and add - M .: OOO "Publishing house Nova wola", 2012. - 1216 p.
2. Hayallah AM, Elgaher W.A., Salem O.I., Alim A.A.A.A. A. Design and Synthesis of Some New Theophylline Derivatives with Bronchodilat or Antibacterial Activity // Arch. Pharm Res - 2011. - V. 34, N 1. - P. 3-21.
3. Hayallah AM, Talhoun A. A., Alim A. A. M. A. Design and Synthesis of New 8-Anilide Theophylline Derivatives as Bronchodilators and Antibacterial Agents // Ibid. - 2012. - V. 35, N 8. - P. 1355-1368.
4. Interaction of methylxanthines and gentamicin against Staphylococcus aureus and Pseudomonas aeruginosa: the role of phosphodiesterase inhibition // Acta Microbiol. Immunol Hung - 2012. - V. 59, N 1. - P. 13-20.
5. Voynikova Yu., Valchevab V., Momekova G. et al. Theophylline-7-acetic acid derivatives with amino acid anti-tuberculosis agents // Bioorg. Med. Chem Lett - 2014. - V. 24, N 14. - P. 3043-3045.
6. Priimenko B. A., Romanenko N. I., Garmash SN, et al. Preparation of 3-methyl-8-bromoxanthine and its alkylation // Ukr. chem journ - 1985. - Vol. 51, No. 6. - P. 660-663.
7. Romanenko MI, Fedulova IV, Pryymenko B.O., Orest'enko L.P. Synthesis and biological activity of 3-methyl-7-alkyl-8-alkyl-, dialkyl-, cycloalkylaminoxanthines // Pharmac. journ - 1986. - No. 5. - P. 41-44.
8. Romanenko N. I., Pehtereva T. M., Cervinsky A. Yu., Etc. Synthesis and PMR-spectroscopic study of 8-acetylhydrazinoxanthines // Ukr. chem journ - 1988. - Vol. 54, No. 12. - P. 1305-1309.
9. Volyansky Yu.L., Gritsenko I.S., Shirobokov V.P. and others. Study of specific activity of antimicrobial drugs. Method. river - K .: State Pharmacological Center MoH Ukraine, 2004. - 38 p.
Published
2018-09-04
How to Cite
Romanenko, M. I., Nazarenko, M. V., Ivanchenko, D. G., Kamyshny, O. M., & Polishchuk, N. M. (2018). Synthesis, physical-chemical and biological properties of 8-aminoderivatives of 7-alkyl-3-methylxanthines. Farmatsevtychnyi Zhurnal, (6), 50-55. https://doi.org/10.32352/0367-3057.6.15.01
Section
Synthesis and analysis of biologically active compounds