4,5-Diaryl-3-aminopyrazole derivatives as analogs of Combretastatin A-4: synthesis and biological evaluation

A series of cis-restricted 4,5-diaryl-3-aminopyrazole derivatives were synthesized and tested for their cytotoxic activity in vitro against five human cancer cell lines (K562, ECA-109, A549, SMMC-7721, and PC-3). Compounds 5a, 5b, 5d, and 6b showed potent cytotoxicity against all tested cell lines. Primary mechanism research on compound 5a indicated that it was a potent inhibitor of tubulin polymerization, arresting cell cycle in G(2)/M phase. The docking research showed the conformation of 5a overlaps well with CA-4 in the crystallized protein complex, suggesting the 4,5-diaryl-3-aminopyrazoles were good mimics of CA-4.