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dc.contributor.advisorCalderón, Angela
dc.contributor.authorAlturki, Mansour
dc.date.accessioned2016-07-26T13:38:38Z
dc.date.available2016-07-26T13:38:38Z
dc.date.issued2016-07-26en_US
dc.identifier.urihttp://hdl.handle.net/10415/5290
dc.description.abstractThe emergence of multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) has increased the demand for the discovery of new antitubercular drugs. The shikimate pathway is essential for the survival of Mycobacterium tuberculosis (Mtb), due to the production of choris¬mate, a precursor for aromatic amino acids but is absent from mammals. Shikimate kinase (SK) the fifth enzyme in the shikimate pathway in Mtb that catalyzes a phosphate transfer from ATP to shikimate, producing shikimate-3-phosphate (S3P) and ADP, and has been considered a promising drug target for tuberculosis drug discovery. The goal of this thesis is to understand the inhibitory mechanism of the most active compounds from a set of 14 oxadiazole-amide and 2-aminobenzothiazole containing synthetic compounds with IC50 values <50 µM against Mycobacterium tuberculosis shikimate kinase (MtSK) using an LC-MS based approach. Chapter one is an overview of tuberculosis pathogenesis and statistics, and it describes the role of the shikimate pathway in M. tuberculosis (Mtb). Additionally, this chapter describes a short revision of specific and non-specific binding to drug targets, Mtb cell wall permeability, and antibacterial activity of 1,3,4-oxadiazole, and 2-aminobenzothiazole scaffolds. Chapter two describes the experimental characterization of M. tuberculosis shikimate kinase inhibitors containing oxadiazole-amide and aminobenzothiazole rings by using LC-MS and other orthogonal confirmatory assays. Chapter three describes the results, discussion and conclusions. Our findings by the use of LC-MS, 1H-NMR, DLS, TEM, and centrifugation assays suggested that these compounds are non-specific inhibitors of MtSK by aggregate formation.en_US
dc.rightsEMBARGO_GLOBALen_US
dc.subjectPharmacyen_US
dc.titleLC-MS based characterization of Mycobacterium tuberculosis shikimate kinase inhibitors containing oxadiazole-amide and aminobenzothiazole ringsen_US
dc.typeMaster's Thesisen_US
dc.embargo.lengthMONTHS_WITHHELD:12en_US
dc.embargo.statusEMBARGOEDen_US
dc.embargo.enddate2017-07-07en_US
dc.contributor.committeeClark, Randall
dc.contributor.committeeDeRuiter, Jack
dc.contributor.committeeSmith, Forrest


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