Synthesis, cytotoxic properties and tubulin polymerization inhibitory activity of novel 2-pyrazoline derivatives

摘要

A series of novel 1-(3',4',5'-trimethoxybenzoyl)-3,5-diarylpyrazoline derivatives were synthesized and evaluated for their cytotoxic properties on different cancer cell lines and tubulin polymerization inhibitory activity. Compounds 6d and 6e exhibited remarkable cytotoxic activity against different cancer cell lines with good tubulin polymerization inhibitory activity. Compound 6d exhibited moderate selectivity toward renal cancer and breast cancer subpanels with selectivity ratios of 3.06 and 5.11, respectively, at the cytostatic activity (TGI) level. Compounds 6e and 6d achieved good tubulin polymerization inhibitory activity with IC 50 values of 17 and 40 μM, respectively. The photomicrographs made for compounds 6d and 6e on cellular microtubules indicated that the cytotoxicity of these compounds can be attributed to their ability to interfere with microtubule assembly. Molecular modeling studies involving compound 6e with the colchicine binding site of α,β-tubulin revealed hydrogen-bonding and hydrophobic interactions with several amino acids in the colchicine binding site of β-tubulin. Novel 1-(3',4',5'-trimethoxybenzoyl)-3,5-diarylpyrazoline derivatives were synthesized and evaluated for their cytotoxic properties on different cancer cell lines and their tubulin polymerization inhibitory activity. The cytotoxicity of compounds 6d and 6e can be attributed to their ability to interfere with microtubule assembly. Molecular modeling studies involving compound 6e revealed hydrogen-bonding and hydrophobic interactions with several amino acids in the colchicine binding site of β-tubulin.