Design, synthesis, X-ray crystal structures, anticancer, DNA binding, and molecular modelling studies of pyrazole–pyrazoline hybrid derivatives

We have designed and synthesized three pyrazole analogs (4, 5a, 5b), pyrazole-based chalcones (6a–6d) and (8a–8h), and N-formyl/acetyl 1,3,5-trisubstituted pyrazoline analogs (7a–7d), (9a–9d). FT-IR, (1)H, (13)C NMR, and mass spectrometry techniques were used to describe the structures of all the synthesized analogs. The single crystal X-ray method was used to identify the molecular structure of derivatives 4 and 5a. All synthesized analogs were screened by MTT assay on two cancer cell lines, the human lung cancer cell line (A549) and cervical cancer cell line (HeLa). Among all compounds, analog 9d demonstrates significant anticancer activity against HeLa (IC(50) = 23.6 μM) and A549 (IC(50) = 37.59 μM). The non-interactive interaction of active compound (9d) with Calf thymus DNA (Ct-DNA) has been investigated through various methods, such as UV-vis absorption, emission, cyclic voltammetry and circular dichroism. The DPPH (2,2-diphenyl-1-picrylhydrazyl) free radical has been used to measure the antioxidant capacity of the pyrazoline derivative (9d). The outcomes showed that active analog has significant antioxidant activity. In addition, MD simulation of the EGFR tyrosine kinase protein–ligand complex was performed at a time scale of 100 ns. The MMGBSA data of ligand–protein complex are showed stable interactions up to 100 ns.