Abstract
Toxoplasmosis is an infectious disease with paramount impact worldwide, affecting many vulnerable populations and representing a significant matter of concern. Current therapies used against toxoplasmosis are based essentially on old chemotypes, which fail in providing a definitive cure for the disease, placing the most sensitive populations at risk for irreversible damage in vital organs, culminating in death in the most serious cases. Antimalarial drugs have been shown to possess key features for drug repurposing, finding application in the treatment of other parasite-borne illnesses, including toxoplasmosis. Antimalarials provide the most effective therapeutic solutions against toxoplasmosis and make up for the majority of currently available antitoxoplasmic drugs. Additionally, other antiplasmodial drugs have been scrutinized and many promising candidates have emanated in recent developments. Available data demonstrate that it is worthwhile to explore the activity of classical and most recent antimalarial chemotypes, such as quinolines, endoperoxides, pyrazolo[1,5-a]pyrimidines, and nature-derived peptide-based parasiticidal agents, in the context of toxoplasmosis chemotherapy, in the quest for encountering more effective and safer tools for toxoplasmosis control or eradication.
Highlights
Infectious diseases continue to represent leading causes of the global burden at social, economic, and public health levels [1,2,3,4]
Malaria-related research has enabled a better understanding of various aspects attributed to the disease, namely those associated with transmission, infection, and progression inside the human host, including related symptoms and molecular mechanisms, leading to the development of prophylactic measures as well as of structure-based and target-based antimalarial drugs [7]
Investments in research related to leishmaniases and toxoplasmosis are far from those accorded to malaria, and most drugs used against these diseases were developed to treat other vector-borne
Summary
Infectious diseases continue to represent leading causes of the global burden at social, economic, and public health levels [1,2,3,4]. Once inside the intermediate host, the oocysts differentiate into fast-spreading tachyzoite forms of T. gondii, which infect all types of nucleated cells, where they reproduce asexually, encysting subsequently in immunoprivileged organs, such as neural and lymphatic tissues, heart, and lungs, under a dormant minimally metabolically active bradyzoite form of T. gondii [11,12] This process consists in a protective mechanism, which allows the parasite to evade the immune system. Immunodeficient individuals are at high risk of developing severe symptoms, including brain damage, since the brain is the most susceptible organ to primary infections and reactivation of toxoplasmosis Another concerning matter to take into account is the vertical transmission of the parasite, which, if left untreated, may critically affect the fetus, causing irreversible and possibly fatal consequences [14]. The main current shortcomings in the available treatment options are their inefficacy against all of the parasitic stages, namely the acute tachyzoite stage and the chronic bradyzoite stage, where reactivation of the disease becomes a possibility, as happens, for example, in ocular toxoplasmosis and in immunosuppressed individuals, the unequal susceptibility and/or resistance of the parasites to the currently available drugs, and, the high prevalence of severe adverse effects from medication to the carrier of the disease [21]
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