Synthesis, characterization, docking and in vitro evaluation of new pyrazole-carboxylate derivatives as...

Pyrazoles and chalcones have been extensively studied over time due to their broad range of therapeutic potentials. In this study, a new series of pyrazole-carboxylate derivatives were synthesized, characterized, and evaluated for their antibacterial, anticancer and anti-inflammatory activities. Among the synthesized derivatives, compound 5a exhibited significant percentage inhibition in colony counting assay. Compound 5c demonstrated significant cytotoxic activity with an IC₅₀ value of 9.91 µg mL^-1, while also exhibiting lower cytotoxicity towards non-cancerous HEK-293T cells (IC₅₀ = 36.31 µg mL^-1), indicating favourable selectivity. Mechanistic studies, including DAPI staining and flow cytometric analysis, indicated that compounds 5c and 5f inhibited cancer cell growth predominantly by inducing apoptosis rather than cell cycle arrest. Anti-inflammatory activity was determined using protein denaturation assay where compound 5f demonstrated promising activity with an IC₅₀ value of 59.37 ± 0.149 µg mL^-1. Furthermore, molecular docking analysis further provided insights into the binding interactions of the derivatives and the targeted protein. In addition, drug-likeness evaluation using swissADME indicates that the compounds satisfied Lipinski's rule of five.