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Title: Synthesis of analogues of dicoumarol and their measurement as inhibitors of NQO1
Author: Obi, Juliana
ISNI:       0000 0004 6495 4508
Awarding Body: University of Manchester
Current Institution: University of Manchester
Date of Award: 2016
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A variety of novel and effective inhibitors of NQO1 was synthesized. The inhibitors were classified as 'asymmetrical' and 'halfway stage' analogues of dicoumarol. The synthesis of these inhibitors was achieved through the application of different techniques such as 'borrowing hydrogen methodology', thermal and microwave irradiation and reductive C-C cleavage using NaBH3CN. One of the most potent analogues was toxic (IC50 = 9.2 ± 0.3 μM) towards the non-small cell lung cancer cell line, A549.A selection of the most potent inhibitors was re-modified as prodrugs in order to improve drug penetration through the barrier of the cell membrane. This was achieved by conjugation with a delivery agent related to the natural product antheminone A. The synthesis involved a multi-step reaction sequence involving the use of natural product (-)-quinic acid as a precursor. A range of prodrugs were synthesized which exhibited toxicity towards the A549 cancer cell line.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Synthesis ; Inhibitors ; Enzyme and MTT assays