Solvent-free approach for the synthesis of 2,4-disubstituted quinolines using zeolites: evaluation of biological activity†

Abstract

A simple one-step heterogeneous catalytic cyclization-based procedure was employed to prepare 2,4-disubstituted quinolines from ketones and 2-aminobenzophenones using Hβ zeolite as a catalyst in solvent-free conditions. Using a variety of substrates, the probabilities and constraints of catalytic activity were studied. Large scale studies validated the viability and effectiveness of scaling up this catalytic system. Furthermore, the catalyst has been employed repeatedly up to five times without any significant loss in its catalytic efficiency. This method provides a fascinating and green approach for synthesizing a broad range of 2,4-disubstituted quinoline derivatives utilizing simple starting materials and a heterogeneous catalyst in optimum reaction conditions. Furthermore, the anticancer potential of the synthesized compounds was evaluated in vitro against the PC-3, H460 and MDA-MB-231 cell lines. Cytotoxicity assays revealed that compounds 3c, 3q, and 3t exhibited significant anticancer activity against PC-3 cells, while compound 3m demonstrated potent activity against MDA-MB-231 cells. In addition, compounds 3d and 3f showed anti-cancer activity in H460 (lung cancer cells). Notably, compound 3aa exhibited broad-spectrum anticancer activity across all three tested cell lines. Further studies demonstrated that the selected compounds induced apoptosis and caused G1 or G2 phase cell cycle arrest, suggesting their potential anti-cancer activity through the regulation of cell cycle progression. Overall, these findings indicate that 2,4-disubstituted quinolines exhibit significant anti-cancer properties in breast, prostate and lung cancer cells.