A review on synthetic strategies and pharmacological studies of pyrimido[4,5-b]quinoline scaffolds

Abstract

Pyrimido[4,5-b]quinoline scaffolds constitute an important class of fused nitrogen-containing heterocycles with significant synthetic and pharmacological relevance. Considerable progress has been achieved in their synthesis through intramolecular and intermolecular cyclization reactions, multicomponent one-pot methodologies, microwave-assisted techniques, mechanochemical approaches, and green catalytic systems. These strategies enable efficient access to structurally diverse derivatives with improved yields, reduced reaction times, and enhanced sustainability. Parallel biological evaluations have revealed a broad spectrum of activities, including antibacterial, antifungal, antimalarial and anticancer effects. Several derivatives displayed notable cytotoxicity against tumor cell lines such as MCF-7, HCT116 and LNCaP, while others demonstrated potent antibacterial and antifungal properties with low MIC values and promising efficacy against Plasmodium falciparum. Notably, some compounds exhibited low micromolar IC₅₀ values underscoring their pharmacological potential. This review provides a focused overview of synthetic methodologies developed for pyrimido[4,5-b]quinolines and their reported biological activities, thereby highlighting their significance as a versatile scaffold in modern drug discovery.