From quinoline to cancer therapy: A systematic overview of its biological mechanisms and therapeutic roles

Abstract

Cancer remains a leading cause of mortality worldwide, presenting a major challenge to global health. Quinolines, a class of nitrogen-containing heterocycles, have proven to be promising compounds for anticancer therapeutic development due to their diverse pharmacological properties, including cytotoxic, antiproliferative, pro-apoptotic, and immunomodulatory effects. This systematic review provides an updated synthesis of the anticancer applications of quinoline-based compounds, including their chemical synthesis, cytotoxic potential, clinical relevance, and biological mechanisms of action. Rigorous literature searching was conducted across multiple databases, identifying studies that evaluated quinoline derivatives using a range of methodologies, including computational modeling, cell-based cytotoxicity assays, 3D tumor spheroid models, and animal models. Quinoline-based compounds express broad-spectrum anticancer potential by acting on multiple cellular targets and pathways. Their mechanisms include inducing mitochondrial apoptosis, inhibiting key oncogenic kinases, modulating epigenetic regulators, damaging DNA, regulating autophagy, and triggering ferroptosis. Overall, this review highlights quinolines as a versatile and promising chemical scaffold for developing multi-targeted anticancer agents. Continued preclinical and clinical research is essential to optimize their efficacy and expand their therapeutic applications in oncology.