Design and synthesis of dihydronaphthalene vascular disrupting agents and indolequinone-based bioreductives.

Cancer remains a deadly affliction for millions across the United States, and the number of new cases is only expected to rise in the years to come. In the field of anticancer research, vascular disrupting agents (VDAs) that preferentially target the tumor vasculature show great promise. The naturally occurring combretastatins, especially combretastatin A-4 (CA4) and combretastatin A-1 (CA1), in suitable prodrug form, have proven to be highly effective VDAs. In this study, efforts were directed towards the synthesis of two combretastatin analogs bearing key features of CA4 on a dihydronaphthalene framework: Oxi 6196 and a beta-dihydronaphthalene analog. In addition to VDAs, another class of exciting anticancer drugs is bioreductive agents that are selectively targeted towards the hypoxic region of tumors. These compounds are chemically reduced selectively and intracellularly to form active cytotoxic compounds. This study also presents the design and synthesis of two analogs of indolequinone-based prodrugs, which can be triggered to release an attached VDA upon bioreductive activation from the 3- or the 2-position, as well as the attempted synthesis of a CA4-tirapazamine bioconjugate drug.

Name thesis:degree_name

M.S.

Level thesis:degree_level

Masters

Grantor

Baylor University.

Year dc:date.issued

2006

Author dc:creator

• Dogra, Abhishek.

Advisor dc:contributor.advisor

• Pinney, Kevin G.

• Antineoplastic agents -- Synthesis.
• Tubulins.
• Organic compounds -- Synthesis.

Statement dc:rights

• Baylor University works are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. Contact libraryquestions@baylor.edu for inquiries about permission.

Language dc:language.iso

en

Handle dc:identifier.uri

https://hdl.handle.net/2104/5018

OAI identifier oai:identifier

oai:baylor-ir.tdl.org:2104/5018