Synthesis of ent-BE-43547A1 Reveals a Potent Hypoxia-Selective Anticancer Agent and Uncovers the Biosynthetic Origin of the APD-CLD Natural Products

Thomas Poulsen reports the synthesis of ent-BE-43547A1 as a hypoxia-selective anticancer agent.

Hypoxia is a state of very low oxygen levels encountered in some areas of solid tumors, which can lead to the development of a more malignant and resistant cellular phenotype poorly responsive to both radiotherapy and chemotherapy. Targeting hypoxic regions in tumors has been proposed as a possible novel therapeutic approach in oncology. The first series of projects from the group of Professor Thomas Poulsen at Aarhus University (Denmark) has been focused on bioactive compounds, notably those with anti-cancer activities. However, the group is also interested in other types of biological activity. The BE-43547 project sprang from studies that were initially focused on the natural depsipeptide rakicidin A, a compound that was previously reported to selectively kill both hypoxic cancer cells and stem-like leukaemia cells. Besides the synthesis of ent-BE-43547A1 the Poulsen group also uncovered the biosynthetic origin of the APD-CLD natural products.

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