Novel Dihydrobenzofuran Derivatives: Design, Synthesis, Cytotoxic Activity, Apoptosis, Molecular Modelling and DNA Binding Studies

Pyrazoline derivatives (3a-3e) and (4a-4e) were designed and synthesized through chalcones (2a-2e) cyclization with NH2NH2/HCOOH and NH2CSNHNH2/CH3COOH, respectively. The molecular structures were elucidated by using various techniques such as UV-visible, FT-IR, H-1, C-13 NMR spectroscopy and mass spectrometry. The purity of all synthesized compounds was checked by the liquid chromatography-mass spectrometry (LC-MS). Single X-ray crystallography was confirmed the molecular structure of analogs (2d, 3e and 4e). Anticancer activity of the all derivatives was screened against human cancer cell MCF-7 and HepG2 cell lines by MTT assay. The results of anticancer activity of novel analogs 2b, 3b and 3e exhibited promising activity against MCF-7 but low toxic against the HepG2 normal cell line. By using a flow cytometry-based technique, the anticancer effectiveness of potent compounds against the MCF-7 cancer cell line was further validated. DNA binding interactions of the novel analogs 3b and 3e were carried out with calf thymus DNA (Ct-DNA) using absorption, fluorescence, circular dichroism and cyclic voltammetry. In silico molecular modelling of pyrazoline derivatives were also studied using Schrodinger-Maestro v2021-2 against tyrosine kinase receptor with PDB ID: 1M17 to explore their best hits. The 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical was used to measure the antioxidant capacity of active pyrazoline derivatives. Using Swiss ADMET software, the ADMET characteristics of pyrazoline derivatives were also investigated. [GRAPHICS] .