Abstract:

Taking thiazolidinone compounds as an example, we discuss the processes leading to the discovery of anti-cancer lead compounds. Using combinatorial chemistry and high throughput screening approaches, we discovered potent compounds against drugresistant cancer cells. Mechanistic studies indicated that these compounds inhibited microtubule formation, caused G2／M arrest in cell cycle, and induced apoptosis and autophagy. The anticancer activity did not depend on the status of P-gp in cells. These compounds had superb membrane permeability and inhibited tumor growth in vivo. Screening them against 60 human cancer cell lines demonstrated broad anti-cancer activities indicating that they will play a significant role in the future of our fight against cancer.
 

Key words: combinatorial chemistry; thiazolidinone; selectivity; anti-cancer