Michael Nutt

1. Thalidomide derivatives as potential agents for treating liver cancer
2. Synthesis of heterocycles using a novel rhodium^II-catalysed tandem/domino approach
3. Application of these methodologies to the total synthesis of natural products

Thalidomide and its commercially available derivatives possess anti-cancer properties and are already used as effective treatments for hematological cancers like multiple myeloma. Using modern transition metal catalyzed cross-coupling reactions, we are able to rapidly generate a library of structurally diverse thalidomide analogues, which can then be assessed for their ability to selectively inhibit liver cancer proliferation. Some of these compounds have demonstrated remarkable activity in in vitro model assays of liver cancer growth/survival and metastasis. Importantly we are now also working to better understand the mode of action of these lead compounds at the molecular level to further fine tune their structure-activity profile.

Globally liver cancer is the 5^th most common cancer, and the 3^rd most common cause of cancer-related deaths. Treatment options are limited and often ineffective – currently only one chemotherapeutic is available, and it is associated with considerable off-target toxicity. We hope that by making drug selectivity a priority in our screening process, we may identify agents that could lead to the development of safer, more effective drugs for liver cancer with less adverse side-effects.