الفهرس 
ContentsOnly 14 pages are availabe for public view
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Abstract
Several studies have reported various pyrazole derivatives with significant anticancer activity. In this work, new series of pyrazole derivatives were prepared including pyrazolopyrimidines, pyrazolotriazines, pyrazolylthienopyridines, and 2-(pyrazolylamino)thiazol-4-ones, based on 3-amino-5-methyl-1H-pyrazole as a synthetic precursor. The synthesis of the target compounds was monitored by TLC, and structure clarification was confirmed by IR, 1H NMR, 13C NMR, mass spectroscopy and elemental analysis. Fourteen compounds were tested in vitro against hepatocellular carcinoma cell line (HepG2). The results revealed that the pyrazolylhydrazonoyl cyanide 111, the pyrazolopyrimidine 106, and the pyrazolylaminothiazolone 120 were the most active with IC50 values of 2.00, 7.00, and 7.00 µM respectively in comparison with 5.5 µM for cisplatin as a reference drug. Interestingly, all the synthesized compounds showed higher selectivity index than cisplatin. DNA binding assay was also carried out to rationalize the mechanism of action of the newly synthesized dervatives. The results revealed that compounds 106, 111, and 120 displaced methyl green from DNA and bound to DNA with % of displacement at 80.98%, 90.41%, and 80.27% respectively in comparison with doxorubicin (% of displacement at 97.22%). Moreover, molecular modeling studies, including docking into DNA minor groove, flexible alignment, and surface mapping, were conducted. Results obtained proved the superior DNA-binding affinity of the most active anticancer compounds.