Theophylline 7- , biological activity

Foods derived from cocoa beans have been consumed by humans since at least 460 to 480 AD. The source of cocoa beans, the species Theobroma, contains a variety of biologically active components. These include the purine alkaloids theobromine, caffeine, and theophylline. Structurally, they are methylated xanthines and, thus, are often referred to as methylxanthines. Theobromine (3, 7-dimethylxanthine) is the predominant purine alkaloid in cocoa and chocolate. Caffeine (1, 3, 7-trimethylxanthine), the major purine alkaloid found in coffee and tea, is found in cocoa and chocolate at about one eighth the concentration of theobromine. Only trace amounts of theophylline (1, 3-dimethylxanthine) are detected in cocoa and chocolate products. 

Three of the most important methylxanthenes are theophylline, theobromine, and caffeine. Methylxanthenes exhibit a similar range of biological activity. 

Among the unsaturated ketonucleosides may be classified the disaccharide derivative 74, which is an analog of the biologically active compound 68c. The key intermediate for the synthesis of this unsaturated ketodisaccharide nucleoside was the partially protected, disaccharide nucleoside 73, which was prepared by two separate routes,56 Treatment of 73 with the Me2SO-acetic anhydride reagent for two days at room temperature afforded 7-[2,3-di-0-benzoyl-4-0-(3-0-benzoyl-2,6-di-deoxy - / - d - glycero - hex - 2 - enopyranosyl - 4 - ulose) - 6 - deoxy - / - d -glycopyranosyl]theophylline (74), isolated crystalline.56... 

The phosphodlesterase i which cleaves cyclic AMP is inhibited by methyl xanthines and it is entirely possible that some or all of the biological activity observed for these inhibitors of cyclic AMP degradation may be due to this action. For example, theophylline has been shown to increase phosphorylase a activity in the isolated heart and potentiate the effects of epinephrine in this assays . 

Molecularly imprinted sorbent assays represent one of the most typical applications of biomimetic use, where imprinted polymers are used as substitutes of natural antibodies in immunoassays. The assays usually involve competitive binding of an analyte with a certain quantity of labeled ligands, in which the labeled ligand unbound is proportional to the analyte added. Because dissociation constants of common imprinted polymers are around 10 6-10 9 M, competitive binding assays could easily be performed. In practice, many molecularly imprinted sorbent assays have been developed for biologically active compounds, including theophylline, diazepam [26], S-propranolol [27], morphine, Leu-enkephalin [28], cyclosporin A [29], yohimbine [30], methyl-a-glucoside [31], corticosteroid [32], atrazine [33, 34], and 2,4-D [35]. 

Moreover DBcAMP did not inhibit the hydrolysis of cAMP by heart phosphodiesterase, indicating a failure to bind to the enzyme. Since DBcAMP is not degraded by the diesterase its biological activity should not be influenced by those materials which either inhibit (theophylline) or stimulate (insulin, nicotinic acid, imidazole) the enzyme. The effect of these compounds on llpolysls produced by DBcAMP has been studied with somewhat conflicting results. Theophylline was found to potentiate DBcAMP-Induced lipolysis24,79 and nicotinic acid inhibited DBcAMP-induced lipo-lysls27,79. Insulin and imidazole have been reported to have either no effect or to inhibit lipolysis induced by DBcAMP. These results are difficult to interpret at this time. 

The purine bases, caffeine, theophylline, and theobromine, yield the corresponding 6-monothio- and 2,6-dithio derivatives upon reaction with LR without a solvent under microwave irradiation. Thionation of the carbonyl groups in the nucleobases of nucleotides leads to interesting special types of thiolactams, which are expected to exhibit modified biological activities. P3u imidine nucleosides are selectively thionated in the 4-position of the nu-cleobase. The mild reaction conditions applied allow the conversion of nucleosides with labile glycosidic bonds, such as 5,6-dihydropyrimidine-(113) and 2, 3 -dideoxynucleosides. Thiononucleosides with unnatural bases (114) or sugar moieties (115), (116) can also be prepared. 

Romerosa A, Bergamini P, Bertolasi V et al (2004) Biologically active platinum complexes containing 8-Thiotheophylline and 8-(Methylthio)theophylline. Inorg Chem 43 905-913... 

Daly, JW, Airalogs of caffeine and theophylline activity as antagonists at adenosine recept< s. In Role of adenosine and adenine nucleotides in the biological system, (eds. Imai, S, Nakazawa, M), Elsevier science BV, Amsterdam, 1991,119-129. 

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