The synthesis, physicochemical and biological properties of 8-amino-7-(2-hydroxy-2-phenylethyl)-3-methylxanthines

M. I. Romanenko, D. G. Ivanchenko, M. V. Nazarenko, M. V. Diachkov, O. M. Kamyshnyi, N. M. Polishchuk

Abstract


The work is devoted to development of the method for the synthesis of 8-amino-7-(2-hydroxy-2-phenylethyl)-3-methylxanthines and the study of their physicochemical and biological properties. Purine derivatives have long been used as antiviral agents (acyclovir, ganciclovir, etc.) in medical practice, and further research to find new antimicrobial and antiviral agents among purine derivatives are justified and promising. Reactions of 8-bromo-7-(2-hydroxy-2-phenylethyl)-3-methylxanthine with the primary and secondary amines proceed when boiling in the aqueous dioxane medium with formation of the corresponding 8-amino derivatives. The structure of the compounds synthesized has been confirmed by the results of elemental analysis and the data of 1H NMR-spectrometry. Proton signals of the uracil moiety of the molecule in the spectra of all compounds are recorded as two singlets of the corresponding intensity in the range of 10.98-10.54 ppm (NH) and 3.38-3.26 ppm (N3CH3). Protons of the substituent in position 7 form several groups of signals with the corresponding intensity. Aromatic proton signals are recorded as multiplets in the range of 7.46-7.18 ppm. The proton signal of the secondary alcohol group is fixed in the form of a doublet at 5.78-5.45 ppm. Intensity, shape and location of other proton signals fully correspond to the structure of the compounds synthesized. For the initial screening study of the new substances synthesized the reference testing cultures of both gram-positive and gram-negative bacteria and fungi, which belong to clinically significant groups of causative agents of infectious diseases that are different by their morphophysiological properties, have been used. 7-(2-Hydroxy-2-phenylethyl)-8-(4-methylpiperidine-1-yl)-3-methylxanthine has exhibited the antimicrobial and antifungal activity against Staphylococcus aureus and Candida albicans, and it is higher than that of the reference drugs – ampicillin and nistatine. The regularities in the "chemical structure – biological activity" relationship have been determined.

Keywords


xanthine; organic synthesis; NMR-spectroscopy; antibacterial; antifungal agents

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References


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DOI: https://doi.org/10.24959/88737

Abbreviated key title: Vìsn. farm.

ISSN 2415-8844 (Online), ISSN 1562-7241 (Print)