Discovery of novel tubulin CBSI (R)-9k from the indanone scaffold for the treatment of colorectal cancer

In view of the serious adverse reactions and clinical toxicity of first line therapy 5-fluorouracil and lack of small molecule therapeutics in colorectal cancer chemotherapy, a series of natural scaffold-based 3-arylindanone derivatives (9a-q) were designed, synthesized and evaluated as tubulin polymerization inhibitors targeting the colchicine site. The most potent colchicine binding site inhibitor (CBSI),