Synthesis of a novel 7-chloroquinoline-sulphocoumarin hybrid: Characterization, ADME profiling and elucidation of its antiproliferative and anti-EMT potential

Abstract

In the present study, the annulation of 4,7-dichloroquinoline and sulphocoumarin led to the efficient synthesis of a novel hybrid molecule. Both 4,7-dichloroquinoline and sulphocoumarin are significant due to their distinct pharmacological properties. Quinoline derivatives, such as 4,7-dichloroquinoline, are well-known for their broad spectrum of biological activities, including antimalarial, antibacterial, and anticancer properties. Sulphocoumarin compounds, on the other hand, have been recognised for their enzyme inhibition and antioxidant activities, which contribute to their therapeutic potential. By combining these two pharmacophores, we aimed to harness and enhance their individual therapeutic effects. The synthesized compound 8 was characterised by FT-IR, NMR (¹H and ¹³C), and mass spectrometry. Additionally, the physicochemical properties of the compound were evaluated through in silico pharmacokinetic analysis. The compound showed notable antiproliferative potential against MCF-7 human breast cancer cells (IC₅₀ = 27.53 ± 0.02 μg/mL). Besides, it reduced MCF-7 cell motility in a concentration-dependent manner. Furthermore, the effect of the hybrid compound on the epithelial-mesenchymal transition (EMT) was evaluated by its ability to modulate MCF-7 cell motility, as well as the expression of major mesenchymal marker genes, such as Vim, Zeb1, Snail, Slug, and TGF-β. The dual action of our synthesized hybrid compound 8 as an anti-proliferative and anti-EMT agent suggests its further characterization in the in vivo models and elucidation of any synergistic activity in combination with established anti-cancer agents.