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The quinolines are a class of synthetic compounds related to quinine , which has a long history of use against malaria. Quinolines are thought to interfere with heme detoxification, which is necessary for the parasite’s effective breakdown of hemoglobin into amino acids inside red blood cells. The synthetic derivatives chloroquine, quinacrine (also called mepacrine ), and mefloquine are commonly used as antimalarials, and chloroquine is also used to treat amebiasis typically caused by Entamoeba histolytica . Long-term prophylactic use of chloroquine or mefloquine may result in serious side effects, including hallucinations or cardiac issues. Patients with glucose-6-phosphate dehydrogenase deficiency experience severe anemia when treated with chloroquine.
| Common Antiprotozoan Drugs | |||
|---|---|---|---|
| Mechanism of Action | Drug Class | Specific Drugs | Clinical Uses |
| Inhibit electron transport in mitochondria | Naphthoquinone | Atovaquone | Malaria, babesiosis, and toxoplasmosis |
| Inhibit folic acid synthesis | Not applicable | Proquanil | Combination therapy with atovaquone for malaria treatment and prevention |
| Sulfonamide | Sulfadiazine | Malaria and toxoplasmosis | |
| Not applicable | Pyrimethamine | Combination therapy with sulfadoxine (sulfa drug) for malaria | |
| Produces damaging reactive oxygen species | Not applicable | Artemisinin | Combination therapy to treat malaria |
| Inhibit DNA synthesis | Nitroimidazoles | Metronidazole, tinidazole | Infections caused by Giardia lamblia, Entamoeba histolytica, and Trichomonas vaginalis |
| Not applicable | Pentamidine | African sleeping sickness and leishmaniasis | |
| Inhibit heme detoxification | Quinolines | Chloroquine | Malaria and infections with E. histolytica |
| Mepacrine, mefloquine | Malaria |
Because helminths are multicellular eukaryotes like humans, developing drugs with selective toxicity against them is extremely challenging. Despite this, several effective classes have been developed ( [link] ). Synthetic benzimidazoles , like mebendazole and albendazole , bind to helminthic β-tubulin, preventing microtubule formation. Microtubules in the intestinal cells of the worms seem to be particularly affected, leading to a reduction in glucose uptake. Besides their activity against a broad range of helminths, benzimidazoles are also active against many protozoans, fungi, and viruses, and their use for inhibiting mitosis and cell cycle progression in cancer cells is under study. B. Chu et al. “A Benzimidazole Derivative Exhibiting Antitumor Activity Blocks EGFR and HER2 Activity and Upregulates DR5 in Breast Cancer Cells.” Cell Death and Disease 6 (2015):e1686 Possible side effects of their use include liver damage and bone marrow suppression.
The avermectins are members of the macrolide family that were first discovered from a Japanese soil isolate, Streptomyces avermectinius . A more potent semisynthetic derivative of avermectin is ivermectin , which binds to glutamate-gated chloride channels specific to invertebrates including helminths, blocking neuronal transmission and causing starvation, paralysis, and death of the worms. Ivermectin is used to treat roundworm diseases, including onchocerciasis (also called river blindness , caused by the worm Onchocerca volvulus ) and strongyloidiasis (caused by the worm Strongyloides stercoralis or S. fuelleborni ). Ivermectin also can also treat parasitic insects like mites, lice, and bed bugs, and is nontoxic to humans.
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