A comprehensive review on the role of nitrogen containing heterocycles in overcoming ABC transporter mediated multidrug resistance in cancer.

The battle against cancer remains a critical challenge in medical science, with traditional and targeted therapies showing limited efficacy, especially in metastatic cases. A significant factor in cancer's resilience is multidrug resistance (MDR) mediated by ATP-binding cassette (ABC) transporters, such as ABCB1, ABCC1, and ABCG2. This review emphasizes the urgent need for novel inhibitors targeting these transporters to overcome MDR. It examines various nitrogen-containing heterocycles, including quinoline, quinazoline, indole, triazole, tetrazole, and pyrimidine, highlighting the important substitutions that enhance their efficacy. For instance, methoxy-substituted tetrahydroquinolines and pyrimido-pyrazoloquinolines have shown promising ABCG2 inhibition. Quinazoline derivatives, particularly those modified at the aniline and piperazine linkers, exhibit dual inhibitory properties. Indole hybrids and pyrimidine-based compounds also demonstrate substantial MDR reversal activity. The development and optimization of these nitrogen-containing heterocycles are crucial for advancing cancer chemotherapy and achieving lasting treatment solutions.