Design, Synthesis and Evaluation of Prodigiosin Analogues as Chemotherapeutic Agents

We are developing new drugs for breast cancer based on a naturally occurring molecule called prodigiosin found in bacteria in our homes and workplaces. Extracts containing prodigiosin were used in the USA from 1893 to 1963 to treat various cancers. However, prodigiosin was too toxic and was withdrawn from the market by the Food and Drug Administration (FDA) in 1963. We have now decreased toxicity 100-fold while maintaining broad anti-cancer activity by chemically modifying prodigiosin. Our goal is to develop prodigiosin-based drugs that have specific selectivity for breast cancer, while reducing general toxicity and side-effects. About 50% of breast cancers have a much greater ability to take in an essential vitamin called folic acid, compared to healthy cells. We will attach a compound similar to prodigiosin to a molecule that looks like folic acid: we expect that the resultant folate-prodigiosin drugs will target breast cancer cells rather than healthy cells. Ideally, this approach should reduce toxicity (side-effects) elsewhere in the body, while killing breast cancer cells more effectively. We will evaluate the compounds using cells from breast cancers, and other cancers, and we will also evaluate how well the compounds penetrate into solid tumours. Funding of this work will pave the way for a completely new avenue for cancer treatment. We anticipate that novel folate-prodigiosin drugs will fill an urgent need for new treatments for so-called triple negative breast cancers, which currently have limited treatment options and poor prognosis. Our continued ownership of our molecules and their applications will be secured (patents) so that clinical potential can be pursued.