Synthesis, physical-chemical and biological properties of 8-R-thioderivatives of 1-benzyltheobromine
Journal Title: Фармацевтичний журнал - Year 2015, Vol 5, Issue 5
Abstract
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.
Authors and Affiliations
D. G. Ivanchenko, M. I. Romanenko, B. A. Samura, V. I. Kornienko
Keywords
Related Articles
- EP ID EP586622
- DOI -
- Views 60
- Downloads 0
Expert research of the efficiency and safety of drugs for the treatment of children with pneumonia
In the modern pharmaceutical science during the development of a number of methodologies and data analysis is using the theory and methodology of processing of expert opinions. That expert assessments are distinguished i...
Analysis of dynamics of the medcine list in the government program «available medicines» for treatment of bronchial asthma
The problem of accessibility for socially significant goods for the population, among which the most important place occupy medicines in Ukraine, is very acute today. In this regard, the need for specific state interfere...
Integrated use of the bark of spindle tree (Euonymus europaea L.). investigation of lipophilic substances
The bark and fruit of European spindle tree (Euonymus europaea L.) has long been used in folk medicine as an anthelmintic, anti-insecticide, as well as for treatment ringworm and eczema. However, what substances responsi...
Morphological and anatomical analysis of Angelica silvestris L. and Angelica arhangelica L. leaves
Angélica’s genus has about 60 species. The most common of them in Ukraine are Angelica archangelica L. and Angelica sylvestris L. The aim of our research has been to investigate the morphological and anatomical structur...
The research of anti-inflammatory activity of 5-(5-bromofuran-2-yl)-4-ethyl-1,2,4-triazole-3-thion S-derivatives
The studing of anti-inflammatory activity of the novel compounds may give rise to the using of safer and more active drugs in the treatment of diseases which are shown NSAIDs. To further study the pharmacological prope...