Sulfonamide-functionalized PCAs showed potent tubulin inhibition, strong anticancer selectivity, low hemolytic activity, and favorable physicochemical properties. Compounds 3 and 5 emerged as lead colchicine-site tubulin inhibitors.
A series of quinoline derivatives was designed and synthesized as novel tubulin inhibitors targeting the colchicine binding site.
Compared with the first line therapy 5-fluorouracil, (R)-9k bound to the colchicine site and showed more potent inhibitory activities against colorectal cancer cells, lower cytotoxicity against normal cells and less cardiotoxicity.
Based on the inhibitory effect of CA-4 analogues and indoles on tubulin polymerization, we designed and synthesized a series of N-((1-methyl-1H-indol-3-yl)methyl)-2-(1H-pyrazol-1-yl or triazolyl)-N-(3,4,5-trimethoxyphenyl)acetamides.
The currently designed molecules demonstrated potential anti-cancer activity by the induction of apoptosis and tubulin polymerization inhibition.