Synthesis and evaluation of inhibitors of cell wall biosynthesis in Mycobacterium tuberculosis
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 discovere...
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| Format: | Thesis (University of Nottingham only) |
| Language: | English |
| Published: |
2016
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| Online Access: | https://eprints.nottingham.ac.uk/35769/ |
| _version_ | 1848795157785214976 |
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| author | May, Terry J. |
| author_facet | May, Terry J. |
| author_sort | May, Terry J. |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | 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. |
| first_indexed | 2025-11-14T19:27:38Z |
| format | Thesis (University of Nottingham only) |
| id | nottingham-35769 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| language | English |
| last_indexed | 2025-11-14T19:27:38Z |
| publishDate | 2016 |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-357692025-02-28T13:31:45Z https://eprints.nottingham.ac.uk/35769/ Synthesis and evaluation of inhibitors of cell wall biosynthesis in Mycobacterium tuberculosis May, Terry J. 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. 2016-12-14 Thesis (University of Nottingham only) NonPeerReviewed application/pdf en arr https://eprints.nottingham.ac.uk/35769/1/Terry%20May%20Thesis%20-%20Synthesis%20and%20evaluation%20of%20inhibitors%20of%20cell%20wall%20biosynthesis%20in%20Mycobacterium%20tuberculosis..pdf May, Terry J. (2016) Synthesis and evaluation of inhibitors of cell wall biosynthesis in Mycobacterium tuberculosis. PhD thesis, University of Nottingham. drug resistance tuberculosis antibiotics |
| spellingShingle | drug resistance tuberculosis antibiotics May, Terry J. Synthesis and evaluation of inhibitors of cell wall biosynthesis in Mycobacterium tuberculosis |
| title | Synthesis and evaluation of inhibitors of cell wall biosynthesis in Mycobacterium tuberculosis |
| title_full | Synthesis and evaluation of inhibitors of cell wall biosynthesis in Mycobacterium tuberculosis |
| title_fullStr | Synthesis and evaluation of inhibitors of cell wall biosynthesis in Mycobacterium tuberculosis |
| title_full_unstemmed | Synthesis and evaluation of inhibitors of cell wall biosynthesis in Mycobacterium tuberculosis |
| title_short | Synthesis and evaluation of inhibitors of cell wall biosynthesis in Mycobacterium tuberculosis |
| title_sort | synthesis and evaluation of inhibitors of cell wall biosynthesis in mycobacterium tuberculosis |
| topic | drug resistance tuberculosis antibiotics |
| url | https://eprints.nottingham.ac.uk/35769/ |