Novel dihydrobenzofuran derivatives: design, synthesis, cytotoxic activity, apoptosis, molecular modelling and DNA binding studies

Abstract

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, ¹H, ¹³C 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 Schrödinger-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.

Communicated by Ramaswamy H. Sarma

Keywords:

• Pyrazoline
• anticancer
• molecular modelling
• Ct-DNA
• antioxidant
• ADMET

Acknowledgment

MR also thanks to CSIR for financial assistance as NET-SRF 09/466(0228)/2019-EMR-I. All simulations were run using Schrödinger-Maestro v2021-2 in the LENGAU cluster hosted by the Centre for High Performance Computing (CHPC) in Capetown, South Africa.

Disclosure statement

Authors have no conflict of interest.

Additional information

Funding

This work was supported by CSIR.