Type
Text
Type
Thesis
Advisor
Drueckhammer, Dale | Ojima, Iwao | Boon, Elizabeth.
Date
2013-12-01
Keywords
Chemistry | cabazitaxel, SB-T-12301, taxane, tumor-targeting drug conjugates
Department
Department of Chemistry.
Language
en_US
Source
This work is sponsored by the Stony Brook University Graduate School in compliance with the requirements for completion of degree.
Identifier
http://hdl.handle.net/11401/77161
Publisher
The Graduate School, Stony Brook University: Stony Brook, NY.
Format
application/pdf
Abstract
Cancer is one of the most serious diseases of the world, leading to one of eight deaths. Although the medical advancements have contributed greatly to the decline of other diseases, treatments for cancer have remained only modestly effective. Traditional chemotherapeutics such as Taxol and Taxotere generally lack specificity, and repeated administration often leads to multi-drug resistance (MDR). To increase the efficacy and specificity of drugs, both the synthesis and evaluation of lead compounds and the development of drug delivery system are equally important. SB-T-1214 and three novel taxanes, SB-T-12301 and two of its analogues, were synthesized by the standard Ojima-Holton coupling protocol using the corresponding β -lactam and 7,10-dimethylated-10-DAB III and C-2 meta-methyl or fluorobenzoyl 7,10-dimethylated-10-DAB III. The β -lactam was obtained via two well-established synthetic routes: Staudinger [2+2] cycloaddition followed by enzymatic resolution protocol and the chiral ester enolate-imine cyclocondensation. In addition, tumor-targeting taxane-based drug conjugate was synthesized by using biotin as the tumor-targeting module and a self-immolative disulfide linker, which can be cleaved in cancer cells due to high concentration of glutathione. Biotin plays a critical role in many biological processes. It is greedily taken up by tumor cells through a process of receptor-mediated endocytosis (RME) to meet its need of fast growth and propagation. The receptors of biotin are highly overexpressed on the surface of tumor cells and making them a good target for tumor-targeting drug design. | 169 pages
Recommended Citation
Wang, Changwei, "Synthesis of SB-T-12301 Analogues and Tumor-Targeting Taxane-Based Drug Conjugates using Biotin as Tumor-Targeting Module" (2013). Stony Brook Theses and Dissertations Collection, 2006-2020 (closed to submissions). 2997.
https://commons.library.stonybrook.edu/stony-brook-theses-and-dissertations-collection/2997