Anti-parasitic drugs

The most important protozoan infection is malaria and this was an early target for medicinal chemical research. The traditional treatment was an extract of the bark of the cinchona tree, which contained the 

Metronidazole (Flagyl) is used for both bacterial (commonly for dental infections) and some protozoan infections, such as amoebic dysentery. Benzimidazoles, such as mebendazole (Pripsen), are an important group of anthelmintics. The most common anti-fungal agents are triazoles such as fluconazole (Diflucan). 

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Neurobiology of Nematode Muscle Ligand-gated Ion-channels and Anti-parasitic Drugs... 

Nirofuran compounds are also effective anti-parasitic drugs. Nifurtimox, for example, is used to treat Chagas disease (caused by Trypansoma cruzi) but has side effects. In exploring the use of alternatives to nifurtimox, Olea-Azar et al. have examined radical formation from two analogues. Radical anions were observed upon electrolytic reduction of the compounds and a nitroxide, believed to be the glutathionyl radical-adduct, was detected upon electrolysis in the presence of DMPO and GSH. Radical adducts were also detected upon incubation of one of the analogues with microsomes from T. Cruzi.m A novel endo-peroxide reductase has been isolated from T. Cruzi. Whereas the flavoenzyme was found to reduce quinones to their semiquinones, nifurtimox underwent a direct, two-electron reduction, without the formation of radicals.129... 

The end of patent cover for most of the modern anthelmintics means that market prices have fallen and therefore funds are lower for investment in research into animal health by pharmaceutical companies. As it is the animal health market that drives any search for anti-parasitic drugs by the pharmaceutical companies, few companies are now looking for modern anti-nematodal drugs and the market size for drugs that kill trematodes and cestodes are such that a search for new drugs cannot be financially justified. Unless a novel anthelmintic that kills nematodes happens to have activity against trematodes or cestodes, it is unlikely that new drugs will become available... 

The pentavalent antimony compound, sodium stibogluconate, is used as an anti-parasitic drug. Treatment of Leishmania braziliensis has been reported to be successful with sodium stibogluconate whereas in Leishmania mexicana, the response was lower and the preferred drug for this disease was ketoconazole . 

McDonald (31) which will serve as useful introductions. A variety of anti-parasitic drugs have been developed and three examples, the benzimidazoles, levamisole and ivermectin will be mentioned briefly here. 

Li XQ, Bjorkman A, Andersson TB, Gustafsson LL, Masimirembwa CM. Identification of human cytochrome P(450)s that metabolise anti-parasitic drugs and predictions of in vivo drug hepatic clearance from in vitro data. Eur J Clin Pharmacol 2003 59 429-442. 

Hanke T, Ramiro MJ, Trigueros S et al. Cloning, functional analysis and post-transcriptional regulation of a type II DNA topoisometase from Leishmania infantum. A new potential target for anti-parasite drugs. Nucleic Acids Res 2003 31(16) 4917-28. 

Padmanabhan PK, Mukherjee A, Singh S et al (2005) Glyoxalase I from Leishmania donovani a potential target for anti-parasite drug. Biochem Biophys Res Commun 337 1237-1248... 

J. Rodrigues da Silva and M. J. Ferreira, "Mode of Action of Anti-parasitic Drugs" in Proc. of the Third Int. Pharmacol. Meeting,... 

Factors in successful treatment with anti-parasitic drugs... 

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