Synthesis and biological evaluation of 3,4-diaryl-5-aminoisoxazole derivatives

A series of cis-restricted 3,4-diaryl-5-aminoisoxazoles have been synthesized and evaluated for their biological activities. Among them, compound 11a and 13a displayed potent cytotoxic activities in vitro against five human cancer cell lines with IC50 values in the low micromolar range and two compounds inhibited tubulin polymerization with IC50 value of 1.8, and 2.1 μM, respectively, similar to that of CA-4. Compound 13a could arrest at the G2/M phase of the cell cycle at the concentration of 0.1 and 1.0 μM and induce apoptosis at 0.1–1.0 μM.

A series of cis-restricted 3,4-diaryl-5-aminoisoxazoles (11a–h, 12a–h and 13a–c) have been synthesized and evaluated for their biological activities. The representative compounds 11a and 13a displayed potent cytotoxic activities and strongly inhibited tubulin polymerization.Figure optionsDownload as PowerPoint slide