Abstract
Thiamine plays a very important coenzymatic and non-coenzymatic role in the regulation of basic metabolism. Thiamine diphosphate is a coenzyme of many enzymes, most of which occur in prokaryotes. Pyruvate dehydrogenase and 2-oxoglutarate dehydrogenase complexes as well as transketolase are the examples of thiamine-dependent enzymes present in eukaryotes, including human. Therefore, thiamine is considered as drug or diet supplement which can support the treatment of many pathologies including neurodegenerative and vascular system diseases. On the other hand, thiamine antivitamins, which can interact with thiamine-dependent enzymes impeding their native functions, thiamine transport into the cells or a thiamine diphosphate synthesis, are good propose to drug design. The development of organic chemistry in the last century allowed the synthesis of various thiamine antimetabolites such as amprolium, pyrithiamine, oxythiamine, or 3-deazathiamine. Results of biochemical and theoretical chemistry research show that affinity to thiamine diphosphate-dependent enzymes of these synthetic molecules exceeds the affinity of native coenzyme. Therefore, some of them have already been used in the treatment of coccidiosis (amprolium), other are extensively studied as cytostatics in the treatment of cancer or fungal infections (oxythiamine and pyrithiamine). This review summarizes the current knowledge concerning the synthesis and mechanisms of action of selected thiamine antivitamins and indicates the potential of their practical use.
Highlights
All living cells and organisms require many organic compounds to sustain metabolic reactions
Despite many years of research, even recently some of the known derivatives of thiamine were used in research to induce experimental conditions similar to the thiamine deficiency in animal models and during the study of functioning of thiamine diphosphate-dependent enzymes and regulation of expression of genes involved in thiamine synthesis
Similar relationship for oxythiamine diphosphate (Ki = 20 μM) was obtained for pyruvate decarboxylase (PDC) from yeast [124] but in the case of pyrithiamine Ki value was higher (78 μM) in comparison with Km for thiamine diphosphate (23 μM). All these results confirm that oxythiamine diphosphate, in contrast with pyrithiamine diphosphate, show a higher affinity to the thiamine diphosphate-dependent enzymes compared with the natural coenzyme
Summary
Thiamine and selected thiamine antivitamins — biological activity and methods of synthesis. Thiamine diphosphate is a coenzyme of many enzymes, most of which occur in prokaryotes. Pyruvate dehydrogenase and 2-oxoglutarate dehydrogenase complexes as well as transketolase are the examples of thiamine-dependent enzymes present in eukaryotes, including human. Thiamine antivitamins, which can interact with thiamine-dependent enzymes impeding their native functions, thiamine transport into the cells or a thiamine diphosphate synthesis, are good propose to drug design. The development of organic chemistry in the last century allowed the synthesis of various thiamine antimetabolites such as amprolium, pyrithiamine, oxythiamine, or 3-deazathiamine. Results of biochemical and theoretical chemistry research show that affinity to thiamine diphosphate-dependent enzymes of these synthetic molecules exceeds the affinity of native coenzyme. This review summarizes the current knowledge concerning the synthesis and mechanisms of action of selected thiamine antivitamins and indicates the potential of their practical use. Accepted Manuscript Online: 05 December 2017 Version of Record published: 10 January 2018
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
