Promising Drug Repurposing Candidates Targeting Free-Living Amoebae: A Systematic and Critical Review of Laboratory-Based Evidence v1

Free-living amoebae (FLA) are opportunistic protozoan pathogens capable of causing severe and frequently fatal infections in humans and animals, including primary amoebic meningoencephalitis, granulomatous amoebic encephalitis, and Acanthamoeba keratitis. Current therapeutic options remain limited, largely empirical, and often associated with high toxicity and inconsistent efficacy. Drug repurposing represents a promising strategy for accelerating the identification of effective anti-FLA therapies by leveraging compounds with established pharmacological and toxicological profiles. This systematic review aims to identify approved drugs evaluated for antiamoebic activity against FLA species in laboratory models and to critically assess their potential for therapeutic repurposing. The review will synthesize evidence from in vitro and in vivo studies, focusing on trophocidal and cysticidal activity, potency, and toxicity parameters under defined ADMET conditions.