Preparation, DFT calculations, docking studies, antioxidant, and anticancer properties of new pyrazole and pyridine derivatives.

Seven novel pyrazole derivatives (4a-g) and four novel starting compounds incorporating substituted pyridine moieties were synthesized successfully. Cell viability assay for the tested compounds was performed, and the inhibitory concentrationlogarithmic 50 (LogIC50 ) values of the compounds were calculated after a 24-h treatment. Four of the examined compounds (3d, 3g, 4f, and 4g) showed comparable cytotoxic activity against CaCo-2 compared to the standard drug docetaxel at 0.1 and 1 μM concentrations. Although the LogIC50  of docetaxel was -0.678 μM for CaCo-2 cells at 24 h, the LogIC50 values of compounds were -0.794, -0.567, -0.657, and -0.498 μM, respectively. Five of the compounds (2d, 2g, 3d, 3g, and 4e) showed comparable cytotoxic activity against MCF-7 at 0.1 μM concentration compared to docetaxel (p < 0.05). Docking studies revealed the compounds have a good affinity to the active site of the human topoisomerase II β enzyme. The antioxidant capacities of all compounds were determined using both 1,1-diphenyl-2-picrylhydrazyl and metal chelation methods. Although the compounds did not show significant antioxidant activity, relatively effective are compounds 3c, 3d, and 3g, which are hydrazine derivatives with approximately 50% antioxidant activity of standard antioxidants at concentrations of 62.5 and 125 μg/ml.