Design, synthesis, and biotechnological evaluation of Thiophene-based chalcones and Δ2-pyrazoline derivatives: Antibacterial, cytotoxic, and molecular docking studies

Abstract

Antimicrobial resistance (AMR) and cancer are among the most extensively studied areas that still require further improvement. In the present study, four new compounds were synthesized via Claisen-Schmidt condensation reaction followed by ring closure, yielding pyrazoline heterocyclic derivatives bearing a thiophene moiety. The compound structures were confirmed using spectroscopic techniques, such as FT-IR, NMR, and GC–MS. These compounds were biologically evaluated for antimicrobial activity against two Gram-positive bacteria (Staphylococcus aureus and Streptococcus pyogenes) and two Gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa), and for anticancer activity against the human cancerous breast cell line (MCF-7). Tested compounds (1–4) exhibited antibacterial activity against the isolate strains, with MICs ranging from 128 to 512 μg/mL and MBCs from 256 to 1024 μg/mL. Compound 2 was the most potent inhibitor against MCF-7, with an IC50 of 46.71 μg/mL (180.17 μM), while the other compounds were less active. Molecular docking against glucosamine-6-phosphate synthase and tubulin indicated favorable binding affinities, with compound 4 showing the strongest predicted binding energies of −8.0 and − 7.4 kcal/mol, respectively. Overall, these results provide structure–property information for thiophene-based chalcone and their 2-pyrazoline scaffolds, and a basis for further optimization.