Synthesis, physical-chemical and biological properties of 8-R-thioderivatives of 1-benzyltheobromine

  • D. G. Ivanchenko Zaporizhzhia State Medical University
  • M. I. Romanenko Zaporizhzhia State Medical University
  • B. A. Samura National Pharmaceutical University, Kharkiv
  • V. I. Kornienko National Pharmaceutical University, Kharkiv
Keywords: synthesis, theobromine, 8-thioderivatives, NMR-spectroscopy, acute toxicity, biological action


Key way for creating new medicinal drugs is structural modification of known and existent natural compounds with high biological activity. In this aspect researchers’ attention is drawn by xanthine derivatives which appear to be antagonists of adenosine receptors, phosphodiesterase inhibitors and histone deacetylase inducers. This resulted in their widespread application in medicine to cure asthma, bronchitis and chronic obstructive pulmonary disease. In addition, xanthine derivatives are used as diuretics, analgesics, heart pacemakers, anti-inflammatory, psychotropic and renal protective agents. 

The aim of this work lies in developing unique methods to synthesize undocumented in other scientific papers 8-thioderivatives of 1-benzylthiobromine and also studying of their physical, chemical and biological properties.

Acute toxicity of synthesized compounds has been studied with the application of Kerber method. The study of diuretic activity of obtained compounds was carried out applying Berkhin method. Analgesic activity of synthesized xanthines was studied at ‘acetic acid writhing’ model. Anti-inflammatory activity was studied at ‘acute aseptic edema’ model. Antioxidant activity was studied in vitro using the method of non-enzymatic initiation of free-radical oxidation.

Heating of 1-benzyl-8-bromotheobromine with double excess of sodium sulphidenonahydrate in dimethylformamide environment results in formation of 8-thiotheobromine. Reactions of thioxanthines with halogenketones and chloroacetamide proceed smoothly with their short-time heating in aqueous alcohol environment.

By applying such computer programs as ALOGPS, DRAGON, GUSAR and ACD/Percepta Platform was established viability of further invitro and invivo research.

Accessible laboratory methods have been elaborated to synthesize 8-thiosubstituted 1-n-methylbenzyltheobromine, their structure having been proved by elemental analysis, PMR-spectroscopy and mass-spectrometry data.

Molecular and pharmacological descriptors to forecast properties of the obtained substances have been calculated, in addition to acute toxicity index.

Also the study of acute toxicity, diuretic, analgesic, anti-inflammatory and anti-oxidant activity of synthesized compounds has been carried out.

After additional research 1-benzyl-8-(2-oxo-2-phenylethylthio)theobromine can be used in medical practice as an antioxidant agent.


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How to Cite
Ivanchenko, D. G., Romanenko, M. I., Samura, B. A., & Kornienko, V. I. (2018). Synthesis, physical-chemical and biological properties of 8-R-thioderivatives of 1-benzyltheobromine. Farmatsevtychnyi Zhurnal, (5), 69-77.
Synthesis and analysis of biologically active compounds