Drug development involves a complex and lengthy process aimed at discovering and developing new treatment methods and drugs for diverse diseases. This process encompasses the identification and evaluation of biological targets, as well as techniques for identifying lead compounds. Mass spectrometry plays a vital role in drug discovery by providing essential information about potential drug candidates. In particular, affinity selection mass spectrometry enables the identification of small molecules that bind with high affinity to biological targets, facilitating the development of more effective and selective drugs. Click chemistry, exemplified by the copper(I)-catalyzed azide-alkyne cycloaddition, serves as a valuable tool for assembling simple molecules into more complex ones, offering an efficient, rapid, and selective synthetic method.
This Master's thesis aimed to develop a strategy for preparing a compound library without isolating individual compounds. The synthesis process consisted of three parts: the preparation of monoazides and diazides, the synthesis of monoalkynes and dialkynes, and the generation of a larger number of 1,2,3-triazoles through the copper(I)-catalyzed azide-alkyne cycloaddition. The formation of triazoles was confirmed using liquid chromatography coupled with mass spectrometry. Additionally, the melting point of the final products (azides and alkynes) was determined, and their inhibitory activity was assessed by testing them on the isolated InhA enzyme. Therefore, affinity selection mass spectrometry was not used, since there was not any active reaction mixture.
Approximately 300 compounds were successfully synthesized within a relatively short timeframe (two months) during the Master's thesis. However, none of the synthesized products exhibited effective inhibitory activity against the InhA enzyme. Future work could involve the use of a larger number of azides and alkynes to increase the likelihood of identifying promising compounds as well as testing the products on other enzymes.
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