1252008-06-2Relevant academic research and scientific papers
Synthesis and in vitro antitumor activity of new 4,5-dihydropyrazole derivatives
Congiu, Cenzo,Onnis, Valentina,Vesci, Loredana,Castorina, Massimo,Pisano, Claudio
experimental part, p. 6238 - 6248 (2010/10/03)
A series of 3,5-diaryl-4,5-dihydropyrazole regioisomers, and their 1-acetylated derivatives, bearing a 3,4,5-trimethoxyphenyl moiety combined with a variety of substituted phenyl rings, was synthesized and evaluated for antitumor activity. Results of the in vitro assay against a non-small cell lung carcinoma cell line (NCI-H460) showed several compounds to be endowed with cytotoxicity in micromolar to sub-micromolar range, depending on substitution pattern and position of aryl rings on 4,5-dihydropyrazole core. Potent and selective activity was also observed in the NCI 60 human cancer cell line panel. 5-(3,4,5-Trimethoxyphenyl)pyrazolines 31 and 39 were found to possess potent antiproliferative activity against SR and MDA-MB-435, with GI50 inhibitory values in nanomolar range. Structure-activity relationships revealed that introduction of a (hydroxy)acetyl group at N-1 of inactive 5-(3,4,5-trimethoxyphenyl)pyrazolines, results in a clear in vitro activating effect. Compound 31 (IC50 = 5.16 μM) showed inhibition of tubulin polymerization comparable to that of CA-4 (IC50 = 4.92 μM).
