diarylquinoline

Diarylquinoline is a class of heterocyclic compounds based on a quinoline core bearing two aryl substituents. These molecules are typically synthetic and designed to explore interactions with biological targets by combining planar aromatic surfaces with varying lipophilicity. The best known member of this class is bedaquiline, a diarylquinoline developed as an antitubercular agent.

The defining mechanism of action for diarylquinolines in medical use is exemplified by bedaquiline, which inhibits the mycobacterial ATP synthase enzyme. By blocking ATP production, bedaquiline disrupts the energy metabolism of Mycobacterium tuberculosis, including persistent bacterial populations, contributing to bactericidal activity. This mechanism differentiates diarylquinolines from many other antitubercular drugs.

Clinical use and regulatory status: Diarylquinolines, most notably bedaquiline, are employed in the treatment of multidrug-resistant tuberculosis as part of combination therapy. Bedaquiline received regulatory approval in several countries based on evidence of accelerated culture conversion and improved treatment outcomes in MDR-TB, and its use is guided by specific safety monitoring and drug interaction considerations.

Safety, pharmacology, and research: Bedaquiline has a long elimination half-life and can cause adverse effects such as QT interval prolongation and hepatotoxicity, necessitating careful patient monitoring. It is metabolized principally by CYP3A4, with potential for drug–drug interactions. Research on diarylquinolines continues, including development of new analogs aimed at improving pharmacokinetic properties, reducing adverse effects, and addressing resistance, while expanding potential antimicrobial applications beyond tuberculosis.