The swift development of bacterial resistance followed soon after revolutionary pharmaceutical progress in the field of antibacterial treatment during the last century. Many antibiotics currently in use are becoming less effective. Nevertheless, research is being focused on the discovery of antibacterial agents that have effect on validated targets via novel mechanisms of action or on new potential targets. Due to the growing resistance against most available antibacterial drugs, it is of utmost importance to develop substances targeting more than one of the essential targets in bacterial cells. Such characteristics are found in some dual inhibitors of the enzymes topoisomerase IV and DNA-gyrase. Both catalyse reactions regarding the interchange of the topological states of the DNA molecule during the replication of the bacterial cell. DNA-gyrase is composed of two GyrA subunits, which are responsible for the decatenation and reunion of the double DNA strands, and of two GyrB subunits containing an ATP-binding site. Our intention was to synthesise new dibromo pyrroleamide derivates of 2-aminobenzo[d]thiazole-6-carboxylic acid as DNA-gyrase B inhibitors. Nevertheless, along our research we gained knowledge about optimal reaction conditions and of isolation procedures required to achieve repeatable synthesis. Furthermore, with given information it will be easier to anticipate feasibility of individual procedural steps along the synthesis of pyrroleamide inhibitors in the future and to predict compatible reaction conditions. Through our research we have attached new fragments of different structure to 4,5-dibromopyrroleamide derivates of 2-aminobenzo[d]thiazole-6-carboxylic acid. We have focused on the optimisation of established interactions between inhibitors and amino acids in the lipophilic pocket of the encyme's ATP-binding site. As it turned out, both of the compounds disintegrated after the attachment of an acetoxy and ethyl acetate fragment on the –OH group of the benzothiazole structure. While we have been able to successfully attach the benzyl fragment, by doing so, we came across additional problems along our reaction procedure. Despite various optimisations of reaction conditions along with isolation procedures, we were not able to produce compounds of proper purity. As we were researching the intermediate steps of our reaction procedure, special attention was paid to the possible creation and characterisation of unwanted side-products. Furthermore, we have focused on the development of optimal reaction conditions, as well as on the design of isolation and purifying procedures that would offer better insight into the most appropriate choice of solvents, considering characteristics of synthesized compounds along individual steps of our reaction procedure. We have achieved optimisation of isolation procedures that would contribute to better yields of individual reactions, as well as of the complete synthesis of pyroleamide inhibitors in the future.
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