Novel pyrazoline-piperazine conjugates as anticancer and antibacterial agents: integrating synthesis, in vitro, QSAR,...

It is a fact that the presence of antioxidants reduces the damage caused by free radicals, which could be linked to cancer development. Antibacterial activity is also linked proportionally to the antioxidant level. So, taking into consideration the above-stated facts, some novel 2-{4-[5-(substituted-phenyl)-3,4-dihydro-2H-pyrazol-3-yl]-phenoxy}-1-[4-(substituted-phenyl)-piperazin-1-yl]-ethanones (9a-z) have been synthesized and were evaluated for their anticancer, antibacterial, and antioxidant potential through established in-vitro and in-silico screening models. In vitro activity, which was performed against human lung cancer cell line 'A549' via MTT assay, established that all the target compounds exhibited potent preferential inhibition, but compounds 9b, 9m, and 9w were found to be the best and most potent cytotoxic agents with an IC₅₀ value of 3.78 ± 0.35 μM, 4.43 ± 0.98 μM, and 7.80 ± 0.55 μM, respectively, considered as approximately more active than doxorubicin with an IC₅₀ value of 9.45 ± 0.32 μM. The same compounds also possess the best antibacterial and antioxidant potential. The in-silico encompassed ADMET, molecular docking, and dynamic simulation studies performed using Molsoft LLC, AutoDock 4.2, and Gromacs applications. The data obtained from the in-silico studies regarding physicochemical parameters, binding affinity, and interactions with targeted proteins such as EGFR, β-ketoacyl-ACP synthase III, and human PrxV reinforced the results of studies in all dimensions.