Design, synthesis and antitumor activity of 3,4,5-Trisubstituted Isoxazoles

In this study, 56 isoxazole derivatives were synthesized and their antitumor activity against 9 cancer cells, such as BXPC-3, MiaPaCa-2, PANC-1, MCF-7, HCT-116, HepG2, NCI-H460, A549 and B16 was detected. The results of pharmacological experiments indicated that most compounds exhibit good cytotoxicity against nine cancer cells. Among them, compound 14 – 3 has an IC 50 of 2.4 μM for colon cancer cells HCT-116, which shows the best effect and is better than the broad-spectrum drug 5-Fluorouracil (5-Fu) for the treatment of colon cancer. In addition, 14 – 3 induces apoptosis and leads to cell cycle arrest in the G2/M phase. Cytotoxicity tests on human normal hepatocytes LO2 also demonstrates that 14 – 3 is less toxic than 5-Fu with no obvious toxicity. These results suggest that 14 – 3 is a potential candidate for the development of anti-tumor drugs. The antitumor activity of 56 novel isoxazole derivatives show that compound 14 – 3 has an IC 50 of 2.4 μM for colon cancer cells HCT-116, which shows the best effect and is better than the broad-spectrum drug 5-Fluorouracil (5-Fu) for the treatment of colon cancer.