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

Abstract

Abstract 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 (LogIC 50 ) 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 LogIC 50 of docetaxel was −0.678 μM for CaCo‐2 cells at 24 h, the LogIC 50 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.