Synthesis of Novel Analogues of the Cytotoxic Natural Product Incarviditone

Abstract

The use of natural products in the development of new pharmaceutical agents is key to the pharmaceutical industry. Incarviditone is one drug candidate that was isolated in 2009 from a natural Chinese plant, Incarvillea delavayi. Incarviditone and its pre-cursor, rengyolone, have shown promising anti-proliferative activity against cancer cell lines. The serendipitious discovery of the biomimetic synthesis has prompted multiple analogues to be synthesised and tested against cancer cell lines. Previously, the Whitehead research group have synthesised analogues of rengyolone and incarviditone with aromatic side chains. The focus of this project was the synthesis of analogues of incarviditone with aliphatic side chains. Described herein is also the synthesis of the opposite enantiomer of the analogues of the incarviditone synthesised. This was to investigate the relationship between the side chains and its anti-proliferative activities. The analogues were tested against A549 non-small-cell lung cancer cell lines in MTT assays. These results were then compared to those of previously synthesised analogues to determine whether there was a relationship between the biological activity of aromatic and aliphatic side chains.

Date of Award	1 Aug 2017
Original language	English
Awarding Institution	The University of Manchester
Supervisor	Roger Whitehead (Supervisor) & Peter Quayle (Supervisor)