A novel green and efficient heterogeneous acid catalyst for the one-pot synthesis of benzopyrazine-aminoimidazole hybrids with antiproliferative potential

Abstract

A novel, green, efficient, and stable magnetically heterogeneous nanocatalyst was developed by immobilizing butanesulfonic acid (BuSO₃H) onto the surface of MFe₂O₄ magnetic nanoparticles (MNPs). The resulting core–shell structure of the MFe₂O₄@PDA@BuSO₃H nanocatalyst was thoroughly characterized using various analytical techniques, including Fourier-Transform Infrared Spectroscopy (FT-IR), X-ray Diffraction (XRD), Energy-Dispersive X-ray Spectroscopy (EDS), Field Emission Scanning Electron Microscopy (FESEM), Transmission Electron Microscopy (TEM), Vibrating Sample Magnetometry (VSM), and Brunauer–Emmett–Teller (BET) analysis. A nanocatalyst was used to synthesize 2-benzopyrazine-aminoimidazole hybrid derivatives through a domino multicomponent Knoevenagel–condensation–cyclization reaction (5a–p) in an environmentally friendly manner. The resulting compounds were then tested for their anticancer activity against three types of human cancer cells (MCF-7, A549, and U87) using the MTT assay. The experiment showed that the nanocatalyst had excellent catalytic activity, and the synthesized compounds exhibited promising antiproliferative activity. Notably, compounds 5g and 5h, containing a 2-naphthyl ring, showed the highest antiproliferative effects against MCF-7 cells, with IC₅₀ values of 0.03 and 0.32 μM, respectively. Additionally, the activity of compounds 5g and 5h in tubulin polymerization, apoptosis induction, and cell cycle arrest in MCF-7 cells were investigated. The results demonstrated that these compounds effectively induced apoptosis and cell cycle arrest. The binding of representative compounds to the colchicine binding site of tubulin was confirmed through molecular modeling studies.