Lung cancer treatment: The total synthesis of ineleganolide
Initial Award Abstract
Both lung cancer and acute myelocytic leukemia (AML) have staggering fatality rates: within five years of diagnosis, 83% of lung cancer patients and 80.5% of AML victims die. Of more than half-a-million cancer deaths last year in the United States, lung cancer ended an estimated 160,440 lives, while leukemia stopped around 23,300. Smoking triggers lung cancer and AML, and is the principal known lifestyle choice that leads to these terminal illnesses. Society must minimize the death toll from these diseases. Organic chemists can contribute by expanding the scope of treatment options. A few compounds show promise in the fight against cancer, molecules like ineleganolide. For patients to benefit from ineleganolide’s potential, this compound must be available in greater quantities.
A few drugs fight both leukemia and lung cancer, medicines including vincristine, doxorubicin, cyclophosphamide, and others. These drugs differ in their modes of action, but all contribute to the fight against both terminal illnesses. Ineleganolide’s mode of activity has not been identified. This compound has a structure unlike that of other drugs on the market, and so may interact in biological systems in ways that other drugs do not. This would open up new windows for lung cancer and leukemia treatment. It is our hope that ineleganolide can join the class of identified medicines to treat those who suffer from either lung cancer or leukemia.
Ineleganolide is a know anti-cancer agent. It is available in such small quantities from nature that it has not been available to be tested against a broad range of cancers. The scarcity of this compound means that isolation from nature is not a viable source for treatment or further study.
The proposed research will construct ineleganolide from inexpensive, readily available starting materials. This study should construct enough of this potent anti-tumor natural product for us to study its mode of action and range of bioactivities. We will prepare molecules that are structurally similar to ineleganolide and submit them for screening against a range of cancers by the National Cancer Institute (NCI). These structurally similar molecules may include simpler drugs that are more potent lung cancer and leukemia treatments. Completion of this project will represent significant progress toward understanding and treatment of two tobacco-related diseases, lung cancer and leukemia. |