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Development of New Potential Antimycobacterial Active Agent Based on the Group of Salicylanilides
Monreal Férriz, Juana ; Vinšová, Jarmila (advisor) ; Opletalová, Veronika (referee) ; Polanc, Slovenko (referee)
Salicylanilides are an important class of aromatic compounds with a wide range of pharmacological activities, such as antibacterial, antifungal and anti-inflammatory, among others. Furthermore; several studies reported their potent antimycobacterial effect. Their activity results from multiple mechanisms. They are therefore interesting compounds for medicinal chemists. As phenolic- containing drugs, we hypothesised that a prodrug approach will make possible the improvement of the pharmaceutical, pharmacokinetic and/or pharmacodynamic properties of salicylanilides. This thesis describes the development of new potential antimycobacterial active agents based on this group that have shown interesting antimycobacterial activity against Mycobacterium tuberculosis, and some atypical strains. As the starting point for our research, the different strategies used in order to overcome the limited bioavailability of phenolic drugs were reviewed. Then new potentially antibacterial active prodrugs of salicylanilides, particularly N-benzyloxycarbonyl-ester and alkyl-carbamate derivatives of salicylanilide, active against M. tbc., MDR-TB strains or non-TB strains such as M. avium and M. kansasii, were prepared. Finally the physicochemical and pharmacokinetic properties of the most active synthesised compounds were...
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