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 ß 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.

Synthesis and anticancer properties of novel hydrazone derivatives incorporating pyridine and isatin moieties.

Nine novel hydrazone derivatives (4a-i) incorporating pyridine and isatin moieties were synthesized through one-pot, four-component heterocyclic condensation reactions. The structures of all new compounds (2a-e, 3a, 3c-e, and 4a-e) were identified by 1 H nuclear magnetic resonance (NMR), 13 C NMR, and Fourier-transform infrared spectroscopic techniques and elemental analysis. Cell viability assays for the tested hydrazone derivatives were performed and the log IC50 values of the compounds were calculated after a 24-h treatment. All hydrazide derivatives tested showed a promising antitumor activity against A-2780 cells as compared with the standard drug docetaxel with a log IC50 value of 0.2200 µM (p < .05). Seven of the examined compounds (4b-e, 4g-i) showed high cytotoxic activity against A-2780 cells as compared with the standard drug docetaxel. Whereas the log IC50 of docetaxel was 0.2200 µM for A-2780 cells at 24 h, the IC50 values of these compounds were -0.4987, -0.4044, -0.8138, -0.3868, -0.6954, -0.4751, and 0.1809 µM, respectively. Three of the compounds, 4b, 4d, and 4i, showed high cytotoxic activity against MCF-7 cells as compared with docetaxel (p < .05). Whereas the log IC50 of docetaxel was 0.2400 µM for MCF-7 cells at 24 h, the log IC50 values of compounds 4b, 4d, and 4i were -0.1293, -0.1700, and 0.2459 µM, respectively.