Identifying Promising Novel Compounds Against Free-Living Amoebae: A Systematic Review of In vitro and in vivo Studies v1

The increasing global incidence of infections caused by free-living amoebae (FLA) and the lack of effective, safe, and approved treatments highlight the urgent need for novel amoebicidal compounds with pharmacological potential. Despite a growing body of literature on the anti-FLA properties of various compounds, comprehensive reviews summarizing this progress remain scarce. This study aimed to identify the most promising compounds tested in vitro and/or in vivo for anti-FLA activity. A systematic review was conducted, analyzing 108 studies published between 1986 and 2024, selected from an initial pool of 23,653 database results. A total of 537 compounds were evaluated for their in vitro anti-FLA activity, with those demonstrating amoebicidal activity ≥50% further analyzed to identify the most promising candidates based on anti-FLA potency and cytotoxicity profiles in non-target mammalian cells.