Antimicrobial Resistance and the Repurposing of Primaquine: A Review of Design, Screening and Antibacterial Evaluation

Abstract

Antimicrobial resistance is now among the most pressing threats to global healthcare. Infections that were once routinely treatable increasingly survive first-line therapy, while the discovery pipeline for genuinely novel antibacterial agents has slowed to a near halt. MRSA is linked to close to 50,000 deaths annually across the United States and Europe, and more than 480,000 cases of multidrug-resistant tuberculosis are recorded in a single year, with projections of roughly ten million deaths per year by 2050 if containment fails. Because bacterial resistance mechanisms — enzymatic drug destruction, efflux, target modification and reduced permeability — are largely directed at specific chemical families, introducing a structurally distinct scaffold is a more promising strategy than further modification of existing classes. Repurposing well-characterised licensed drugs offers a faster route to such scaffolds. Primaquine, an 8-aminoquinoline antimalarial licensed since 1952, is an attractive starting point: its free terminal primary amine provides a convenient synthetic handle for constructing new ring systems while leaving the quinoline core intact.