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  • Synthesis of n-phenyl-pyrrolamides with an oxygen-substituent as DNA gyrase-B inhibitors = Sintesi di n-fenil-pirrolamidi con un sostituente ossigenato come inibitori della DNA girasi B : Mestrado Integrado em Ciências Farmacêuticas
    Meloni, Susanna
    Unfortunately, antibacterial resistance is growing at dangerously high levels in all parts of the world. The increase rates of morbidity and mortality caused by this phenomenon, associated with the ... low number of new approved antibacterial drugs in the last decades, has led to discovery and development of new potential antibacterials. As it has been clinically validated by novobiocin, an interesting target for the design of new antibacterial drugs is ATP binding site of DNA gyrase B, a subunit of bacterial DNA gyrase, member of the family of Topoisomerases II, as well as Topoisomerasis IV, that are functions vital to DNA replication, repair and decatenation. Currently, no drugs, in clinical use, have this enzyme as a target. Basing on structure-based design of previously synthetized molecules, new N-phenyl-3,4-dichloro-5-methyl-pyrrolamides with an oxygen substituent have been synthetized and evaluated them against DNA gyrase from Escherichia coli. Several compounds were also evaluated against the structurally and functionally similar enzyme, topoisomerase IV from Escherichia coli, and against DNA gyrase from Staphylococcus aureus. In the design of the present series, the focus was on the optimisation of biological activities of compounds, varying the properties and the size of substituents at the 3-position. The most active compounds, 19 and 38, had an IC50 of 2.3 nM and 0.75 nM, respectively, against Escherichia coli DNA gyrase. The IC50 values against Staphylococcus aureus DNA gyrase, and E. coli topoisomerase IV were weaker. Antibacterial activities of most potent compounds of this series were evaluated against five Gram-positive and five Gram-negative bacterial strains. Interesting results were obtained again from the compounds 19 and 38, which showed a good inhibitory activity against Klebsiella Pneumoniae, a Gram-negative bacterium, with MIC values in the low micromolar range (19, MIC = 0.25 [micro]g/mL; 38, MIC = 0.5 g/mL). These results have shown that the introduction of certain substituents at 3-position can greatly improve the inhibitory activity of this series of molecules.
    Vrsta gradiva - magistrsko delo ; neleposlovje za odrasle
    Založništvo in izdelava - Cagliari ; Ljubljana : [S. Meloni], 2020
    Jezik - angleški
    COBISS.SI-ID - 17926403

Nobena knjižnica v sistemu COBISS.SI nima izvoda tega gradiva.
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