SYNTHESIS OF FLUORO AND NITRO PYRAZOLINE DERIVATIVES: ANTICANCER AND MOLECULAR DOCKING STUDIES.

A series of novel fluoro and nitro pyrazoline derivatives (3a‐3f and 4a‐4e) was synthesized and characterized using various spectroscopic techniques. Initially, the Claisen‐Schmidt condensation reaction was used to synthesize chalcone derivatives. The reaction between 5‐bromo‐2‐acetyl thiophene with various substituted pyrazole aldehydes in the presence of PEG‐400 (green solvent) gives a high yield of chalcones. Further, pyrazoline derivatives were synthesized by a reaction between 3‐F and 3‐NO₂ phenylhydrazine with synthesized chalcones in reflux conditions. In vitro cytotoxicity screening was carried out for the series against breast cancer (MCF‐7) and lung adenocarcinoma (A549) cells. The MTT assay reveals that compounds 3e and 4c demonstrate good cytotoxicity against MCF‐7, while 3d and 4b showed substantial inhibition of A549 cells. Flow cytometry analysis with 3e, 4c, 3d, and 4b indicates that these induce cell cycle arrest at the G1/S phase, leading to decreased cell proliferation and cell death. Further, mechanistic studies unveil that these compounds trigger apoptosis. In the PARP inhibition assay, 4c showed considerable inhibition compared to pamiparib. Molecular docking studies further support this by revealing a high binding affinity of 4c for the PARP enzyme. The results suggest that pyrazoline derivatives have the potential to be developed into effective anticancer agents.