A streamlined method to synthesize molecules that look and act like natural products is presented this week in Nature Chemical Biology. The molecules’ ability to manipulate mitosis in cells is useful for scientists trying to understand regular cellular functions and the development of cancer.Kamal Kumar, Herbert Waldmann and colleagues drew on a class of natural products—indole alkaloids—as their structural inspiration for creating a focused set of synthetic molecules. The authors created a synthetic method where 12 distinct reactions occurred in a single pot, yielding highly complex multi-ring compounds varying in six places around the molecule. With 26 different molecules in hand, they then tested to see if the molecules had any effect on cells. Like the indole alkaloids the synthesized compounds were meant to mimic, the new structures did impact mitosis. Two centrosomal proteins, nucleophosmin and Crm1, were targeted by these compounds. As nucleophosmin is involved in the establishment of cancer, yet its specific role is not well understood, these compounds could provide valuable insights into the function of this protein in normal and diseased cells.
doi: 10.1038/nchembio.758 | Original article
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