The synthesis of chemical libraries is a fundamental tool used to identify molecules with
desirable biological activity. Recent developments in combinatorial synthesis techniques have
allowed for the rapid generation of very large and diverse chemical libraries that can be used in
conjunction with high-throughput screening (HTS) technology to identify lead molecules that
can be potentially developed into pharmaceuticals. Libraries based around an oxindole scaffold
(previously identified as inhibitors of cRAf1 kinase) were recently shown to display inhibitory
effects against aminoglycoside phosphotransferases (APH) enzymes found in bacteria
responsible for antibiotic resistance to aminoglycosides. Additionally, substituted quinazolines
(similar in structure to the known drug Lapatinib) were identified as a potent inhibitor of both
APH(2”)Id and ANT(2”). The present thesis involves the development of synthetic protocols
suitable for the generation and subsequent biotesting of chemical libraries based around these
hits in order to determine the pharmacophore in each case. / Thesis / Master of Science (MSc)
| Identifer | oai:union.ndltd.org:mcmaster.ca/oai:macsphere.mcmaster.ca:11375/20269 |
| Date | January 2016 |
| Creators | Leckett, Kyle |
| Contributors | Capretta, Alfredo, Chemistry and Chemical Biology |
| Source Sets | McMaster University |
| Language | English |
| Detected Language | English |
| Type | Thesis |
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