| Author: | Zhu, Xuezhen |
| Title: | Chemical modulation of multidrug resistant proteins by triazole bridged flavonoid dimers |
| Advisors: | Chow, Larry (ABCT) |
| Degree: | Ph.D. |
| Year: | 2019 |
| Subject: | Hong Kong Polytechnic University -- Dissertations ATP-binding cassette transporters Drug resistance |
| Department: | Department of Applied Biology and Chemical Technology |
| Pages: | 388 pages : color illustrations |
| Language: | English |
| Abstract: | The central theme of this thesis is the exploration of new modulators of ABC transport proteins by the design and synthesis of a series of triazole-bridged flavonoid dimers. Chapter 1 briefly introduces the background of multidrug resistance, ABC transport proteins, click chemistry as well as the objective of this thesis. Chapter 2 describes a rapid generation of a flavonoid dimer library using "click chemistry". Following this, a high-throughput screening led to the discovery of some highly potent and safe MRP1 modulators is presented. Chapter 3 elucidates the design and synthesis of a series of triazole bridged flavonoid heterodimers and homodimers. Besides, the compounds are evaluated for their potency in reversing BCRP-mediated multidrug resistance. Structure activity relationship of flavonoid dimers towards modulating BCRP is discussed. Finally, a homodimer, Ac22Az8, as a non-cytotoxic, potent and selective BCRP modulator is presented. Chapter 4 describes the design and synthesis a series of triazole bridged flavonoid heterodimers. Following this, the compounds evaluated for their potency in reversing multidrug resistance in P-gp, BCRP and MRP1. Chapter 5 describes the summary future work of this thesis. |
| Rights: | All rights reserved |
| Access: | open access |
Files in This Item:
| File | Description | Size | Format | |
|---|---|---|---|---|
| 991022289512503411.pdf | For All Users | 12.29 MB | Adobe PDF | View/Open |
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