Bisquinoline as a promising scaffold in anti-infective drug discovery: the current state of the art and future prospects.

Introduction: Bisquinoline is a privileged pharmacophore in medicinal chemistry due to its diverse biological activities, particularly against infectious diseases such as malaria, tuberculosis, leishmania, fungi, bacteria, protozoa, schistosomiasis, and HIV. The success of piperaquine, a bisquinoline-derived antimalarial, has underscored its therapeutic potential, driving interest in its role as a small-molecule probe for targeting critical disease pathways. As drug resistance increases and the need for effective treatments rises, bisquinoline's broad pharmacological profile presents promising drug discovery opportunities.

Areas covered: This review explores research on bisquinoline derivatives as anti-infective agents, focusing on synthetic approaches, detailed structure-activity relationships, and therapeutic applications. It includes detailed insights into piperaquine, the only approved bisquinoline drug, based on literature from 2000 to 2025 sourced from PubMed, Scopus, and Web of Science concerning 'bisquinoline scaffold' keywords.

Expert opinion: In the last two decades, significant progress has been made in developing bisquinoline derivatives with various pharmacological effects. These advancements have expanded our understanding of the scaffold's pharmacological diversity and its potential for creating more effective drugs with fewer side effects. This continued progression will aid the development of the next-generation of bisquinoline-based therapeutics.