Infections still represent one of the leading causes of death in the world despite some successful antibiotics available. Due to the increasing resistance of bacteria, compounds with novel mechanisms of action are urgently needed in the fight against bacteria. One of the possible targets for antibacterial activity is the enzyme family Mur ligases (MurC-MurF) that are involved in the biosynthesis of peptidoglycan, an essential component of the bacterial cell wall. In the thesis, we wanted to prepare new potential inhibitors of MurD, which is an enzyme responsible for the attachment of amino acid D-Glu in the nascent peptide chain of UDP-MurNAc-pentapeptide, the precursor that is incorporated into the preexisting peptidoglycan. The design of new compounds was based on the structure of known inhibitors that have been chemically modified by the introduction of hydroxamic acids. We synthesized three final compounds and measured their inhibitory activities on the MurD enzyme isolated from Escherichia coli. Compound methyl 2-(6-butoxynaphthalene-2-sulfonamide)-4-(hydroxycarbamoyl) benzoate (13) proved to be effective. We also tried to synthesize an inhibitor possessing catecholate-type siderophore to improve passage through the bacterial membrane synthesis but unfortunately the synthesis was not successful.
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