Design, synthesis, and bioevaluation of pyrazolo[1,5-a]pyrimidine derivatives as tubulin polymerization inhibitors targeting the colchicine binding site with potent anticancer activities

A series of Pyrazolo[1,5-a]Pyrimidine analogs were designed and synthesized as novel tubulin inhibitors. Among them, compounds 1a and 1b showed the highest antiproliferative activity against a panel of cancer cell lines with average IC50 values of 24.8 nM and 28 nM, respectively. We determined the crystal structures of 1a and 1b in complex with tubulin and confirmed their direct binding to the colchicine site. Compounds 1a and 1b also...