Overview of the antiprotozoal activities of aldehyde-based compounds

The diseases induced by these parasites in humans and animals span a broad spectrum, ranging from mild diarrhea to death, with outcomes heavily dictated by the interplay of parasite traits and host characteristics. This review systematically evaluates the antiprotozoal potential of aldehyde-based compounds through a comprehensive analysis of natural products, synthetic derivatives, and endogenous lipid peroxidation-derived species. A structured literature search was conducted across Web of Science, SciFinder, PubMed, Google Scholar, ACS, and ScienceDirect. The findings are organized into a conceptual framework covering four key areas: sources of antiprotozoal aldehydes, activity profiles against major protozoan taxa (including Plasmodium, Toxoplasma, Leishmania, and Trypanosoma), and emerging broad-spectrum candidates. The mechanistic landscape of aldehyde-based antiprotozoals is multifaceted, frequently involving covalent engagement with parasitic targets. This Janus-faced nature presents a trade-off: covalent inhibition on one hand versus metabolic instability, non-selective cytotoxicity, and suboptimal pharmacokinetics on the other. To address this challenge, we delineate four interconnected strategies. Together, these strategies provide a framework that transforms the intrinsic reactivity of aldehydes-from a barrier to drug development-into a precision tool for overcoming resistance and addressing the limitations of current protozoan therapies.