Thiophene-based N-phenyl pyrazolines: Synthesis, anticancer activity, molecular docking and ADME study

This investigation aimed to synthesize and evaluate the anticancer potential of thiophene-based N-phenyl pyrazoline derivatives containing methoxy groups using both in vitro and in silico assays. The N-phenyl pyrazolines were synthesized by reacting phenylhydrazine with chalcone derivatives. Using the 3-(4,5-dimethyl thiazole-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, we assessed the anticancer activity of the compounds that were synthesized in vitro against four human cancer cell lines (4T1 and T47D for breast cancer, HeLa for cervical cancer, and WiDr for colorectal cancer), as well as a normal cell line (Vero). The in silico evaluation was carried out through molecular docking and absorption, distribution, metabolism, and excretion (ADME) prediction. Among the synthesized pyrazolines, pyrazoline 2 was revealed as the most active anticancer against 4T1, HeLa, and WiDr cancer cell lines, with IC50 values of 9.09, 9.27, and 0.25 μg/ml, respectively. Furthermore, pyrazoline 2 showed high selectivity with selectivity index values of more than 6 toward all tested cancer cell lines. In silico evaluation via molecular docking against epidermal growth factor receptor revealed that pyrazoline 2 had the lowest binding energy with a value of 8.8 kcal/mol, which was consistent with experimental data. The ADME study using the pkCSM webtool indicated that the N-phenyl pyrazoline derivatives had good pharmacokinetic properties. Therefore, the results of this study suggest that thiophene-based N-phenyl pyrazoline derivatives containing methoxy groups, especially pyrazoline 2, could be potential anticancer agents.