Benzimidazole-Quinoline Hybrids: Synthesis and Antimicrobial Properties

<b>Background</b>: Heterocyclic compounds are particularly important in medicinal chemistry. With a range of therapeutic uses, benzimidazoles and quinolines are both key heterocycles in medicinal chemistry. A number of hybrid heterocyclic compounds have been reported in recent years because they typically have better therapeutic properties than single heterocyclic rings. <b>Methods</b>: A literature search was conducted across relevant scientific literature from peer-reviewed sources, using keywords, including "benzimidazole", "quinoline", "benzimidazole-quinoline hybrids", "antibacterial", "antifungal", "antimalarial" and "hybrid complexes". <b>Results</b>: This review summarizes the synthetic methodologies for benzimidazole-quinoline hybrids, benzimidazole- quinolinones, and benzimidazole-quinoline metal complexes, along with their antimicrobial and antimalarial activities and the reported structure-activity relationship (SAR) studies. The importance of halogen substitution, particularly with chlorine and fluorine atoms, as well as the structure of the linker between the benzimidazole and quinoline rings-specifically chain length, the presence of oxygen, sulfur, or nitrogen atoms, and heterocyclic moieties-is highlighted. A series of benzimidazole-quinoline hybrids exhibit antimalarial and antitrypanosomal activities or show enhanced antimicrobial properties due to the incorporation of a five-membered heterocycle in addition to the two existing heterocyclic rings. Notably, several hybrids from different compound series exhibit very low minimum inhibitory concentrations (MICs) in the range of 1-8 µg/mL, along with low cytotoxicity, supporting their potential for further investigation as antimicrobial agents. <b>Conclusions</b>: This review summarizes the synthetic methods, medicinal properties, and structure-activity relationship (SAR) studies of benzimidazole-quinoline hybrids reported between 2002 and 2026.