Design, synthesis, anticancer activity, and molecular docking study of some thiophene-based pyrazoline derivatives

Abstract

A series of thiophene-based pyrazoline derivatives, designated as 5a-5e was synthesized as potential anti-cancer agents. The first step of the synthetic route involves the preparation of chalcone intermediates through Claisen Schmidt reaction of 2-acetylthiophene with substituted aldehydes. The target compounds 5a-5e were obtained by the cyclization reaction of chalcones with phenylhydrazine and glacial acetic acid as solvent. The new compounds exhibited favorable binding affinities with the epidermal growth factor receptor tyrosine kinase domain (Protein Data Bank ID: 4HJO), as shown by their docking scores between -8.0 and -8.8 kcal/mol, whereas erlotinib showed a binding affinity of -8.0 kcal/ mol. The MCF-7 breast cancer cell line was used to test the anticancer activity of thiophene-based pyrazoline derivatives 5a-5e. Absorption, distribution, metabolism, and excretion analysis showed that synthesized derivatives (5b-5e) have good theoretical pharmacokinetics and drug-likeness characteristics, with no violations of Lipinski's rule of five, signifying their suitability for oral administration whereas 5a showed one violation.. KEYWORDS :Anticancer activity, Molecular docking, Thiophene-based pyrazolines, Tyrosine kinase inhibitor.