Synthesis of new pyrazolidines by [3+2] cycloaddition: Anticancer, antioxidant activities, and molecular docking studies

Abstract

A series of novel pyrazolidine derivatives 2a-j from N-acyl hydrazones 1a-j were designed and synthesized by N-triflylphosphoramide (NTPA) catalyzed [3 + 2] cycloaddition. The structural elucidation of synthesized compounds was carried out using a variety of spectroscopic methods, including IR, 1H and 13C NMR, MS, and elemental analysis. Cytotoxic activity of the pyrazolidine derivatives 2a-j was evaluated against human lung cancer (A549), pancreatic cancer (PANC 1), prostate cancer (DU-145), breast cancer (MCF-7), and in human dermal fibroblast (HDF) by MTS assay. The compounds 2f (IC50= 12.5 μM) and 2g (IC50= 21.8 μM) showed higher antiproliferative activity than all other compounds against the A549 human lung cancer line and PANC1 pancreatic cancer line, respectively. The antioxidant potential of the new pyrazolidines 2a-j was evaluated by the 2,2-Diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity assay. Compounds 2a, 2d, and 2j were found to exhibit significant antioxidant activity compared to standards. Through molecular docking studies, the antiproliferative properties of the novel pyrazolidine compounds 2a–j were studied, and the interactions between the ligand and the protein were determined for the most active compounds, 2f and 2g.