Please use this identifier to cite or link to this item:
http://hdl.handle.net/10397/85421
Title: | Chemical modulation of multidrug resistant proteins by triazole bridged flavonoid dimers | Authors: | Zhu, Xuezhen | Degree: | Ph.D. | Issue Date: | 2019 | 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. | Subjects: | Hong Kong Polytechnic University -- Dissertations ATP-binding cassette transporters Drug resistance |
Pages: | 388 pages : color illustrations |
Appears in Collections: | Thesis |
Access
View full-text via https://theses.lib.polyu.edu.hk/handle/200/10226
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.