Recent Advances in Synthetic Quinoline-Based Compounds in Anticancer Drug Design

Compounds based on the quinoline (benzo[b]pyridine, 2,3-benzopyridine, or 1-azanaphthalene) core demonstrate extensive biological functionality. In recent years, scientific interest has converged on their antitumor properties, where they trigger antiproliferative responses through a variety of mechanisms, including the targeting of distinct signaling cascades. To overcome the limitations of high-specificity targeted therapies such as tumor resistance, recent research has shifted toward multi-target therapeutic strategies. The lack of strict drug specificity may be an advantage, offering improved pharmacodynamics. Compared to highly specific therapies, this multi-target strategy potentially may reduce the risks of cancer resistance. This review provides a comprehensive analysis of recent studies on the most critical targets for anticancer quinoline-based derivatives, detailing their mechanisms of inhibition or activation across various proteins, enzymes, and signaling pathways. These targets span receptor tyrosine kinases as well as cell-surface receptor complexes and integrin signaling modules. Inside the cell, quinolines modulate intracellular signaling and nuclear transcription factors alongside epigenetic factors. Furthermore, these compounds dictate cell cycle regulation and mitotic arrest. They also influence DNA integrity and post-translational modifications. Finally, quinolines address tumor microenvironment adaptation and efflux-mediated resistance. A wide array of anticancer activities indicates that quinolines may inhibit tubulin polymerization and induce apoptosis via caspase, or ROS-mediated pathways. Finally, due to the presence of aromatic nitrogen atoms, the quinoline derivatives constitute appropriate ligands that may be employed in the development of metal complexes. It has been demonstrated that such compounds, including 8-hydroxyquinoline-containg ligands, possess exceptional coordination abilities and transition metal recognizing properties. Various quinoline chelates containing calcium, nickel, zinc, ruthenium, hafnium, or silver possess improved anticancer properties which place them in a leading position for the development of effective chemotherapeutic agents. Given the vast amount of literature, this review summarizing the recent developments on synthetic quinoline-containing compounds and their metal complexes with proven anticancer properties is restricted to the short period with an emphasis on the 2025–2026 literature, while including essential background from earlier recent work (2022–2024).