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Title: Synthesis and evaluation of inhibitors of cell wall biosynthesis in Mycobacterium tuberculosis
Author: May, Terry J.
ISNI:       0000 0004 5990 6157
Awarding Body: University of Nottingham
Current Institution: University of Nottingham
Date of Award: 2016
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The emergence of drug-resistant strains of tuberculosis has led to a demand for the development of new antibiotics. One new target is the cell wall biosynthesis enzyme UDP-Galp mutase (UGM), which aids the formation of the bacteria’s characteristic mycolic acid cell wall. LQ10 and LQ6 were discovered through a library screen. The synthesis of LQ10 was achieved along with 4 analogues. Another class of compounds, 2-aminothiazoles, were produced. Thirteen of these compounds were produced and along with the LQ10 analogues, initially gave encouraging results in silico. To test their biological activity, a fluorescent probe was synthesised for use in a high-throughput fluorescence polarization (FP) assay against UDP-Galp Mutase which was expressed from E. coli. The compounds were screened using the fluorescence polarisation assay initially at a concentration of 50 µM, 9 of which demonstrated >70 % inhibition of UGM. Two of which had inhibition greater than 90 %. These preliminary results suggest that some of these compounds are, and can be developed into potent UGM inhibitors. However, it should be noted that these are only single-point results due to limitations in the quantity of UGM available, and that these will need be repeated in triplicate to determine any errors and give more reliable values.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: QP501 Animal biochemistry ; QR 75 Bacteria. Cyanobacteria