Total Synthesis and Structure-Activity Studies of a New Anti-Cancer Drug Based on the Natural Product, Imbricatine

With an estimated 159,900 new cancer cases and 72,200 deaths from cancer predicted to occur this year alone in Canada, the need for new cancer therapies with unique mechanisms of action is urgent. Researchers are finding a promising resource among the ocean’s estimated one to two million structurally diverse microbial species. Compounds derived from marine organisms offer great potential in the fight against cancer; in the past decade, more than 30 natural products from the ocean have entered preclinical and clinical trials as potential treatments for cancer. However, it is often not ecologically or economically feasible to extract the active ingredient by harvesting natural sources in the ocean. Synthetic organic chemistry – where molecules are engineered in the laboratory – serves as an alternative source of these compounds. Inhee Cho is focusing on the synthesis of imbricatine, a chemical originally isolated from the Pacific sea star that shows significant anti-tumour properties. The structural core of imbricatine includes tetrahydroisoquinoline, a molecular structure that is also found in many biologically active agents, including anti-tumour antibiotics and drugs that treat diseases such as asthma, Parkinson’s and other nervous system diseases. Cho is developing an efficient way to synthesize tetrahydroisoquinoine, allowing rapid access to this important class of natural products in order to obtain enough material for biological testing and chemotherapy. Cho’s work may facilitate the discovery of new lead compounds with useful pharmacological properties, potentially leading to new therapies for treating cancer