Plasmodium spp

Frey TG, Perkins GA, Ellisman MH (2006) Electron tomography of membrane-bound cellular organelles. Annu Rev Biophys Biomol Struct 35 199-224 Fry M, Beesley JE (1991) Mitochondria of mammalian Plasmodium spp. Parasitol 102 17-26... 

Artemisinin (Fig. 10.1) is a highly phytotoxic sesquiterpene endoperoxide,12 found only in the glandular trichomes of Artemisia annua,11 Duke et a/.13 first tested it for phytotoxicity because of its high level of activity against malarial parasites (Plasmodium spp).23 Others later verified that it is strongly phytotoxic.3,4,30 These studies showed little more than that the compound is highly phytotoxic. Chen and... 

Enzymes that are addressed by major drugs have been studied in particular detail. Thus, well above one hundred stmctures have been reported for dihydrofolate reductases from a variety of organisms, including major pathogens such as Mycobacterium tuberculosis, which is the causative agent of tuberculosis, and of Plasmodium falciparum, which is the most important of the Plasmodium spp. that causes malaria. The interaction of mammalian dihydrofolate reductases with inhibitors that are used as cytostatic agents and/or immunosuppressants is also documented extensively by X-ray stmctures. 

Dapsone Co-factor synthesis Unique target Plasmodium spp. 

Proguanil Co-factor synthesis Differences in the target Plasmodium spp. 

Chloroquine Nucleic acid synthesis Differential uptake Plasmodium spp. 

A number of other 7-chloro-4-substituted quinolines (16-20) have also been synthesized as structural analogues of chloroquine [26]. Of these 14153-RP (17), 12494-RP (18) and tripiperaquine (M-1020, 20) showed promising activity against Plasmodium spp. in laboratory animals [26]. 

Later as a result of the investigation of Archibold and Ross [33a] and others, it has been shown that dapsone (and its repository forms) could clear the blood from trophozoites of different plasmodium spp. The sensitivity of the different species of parasites varied P. falciparum is very sensitive, while P. vivax is less so. Their action, as with sulphonamides, is mainly against the blood stages with marginal activity against primary (pre-erythrocytic) tissue forms and no activity against sexual and latent tissue forms. It has also been shown that dapsone potentiated the action of pyrimethamine, and a combination of the two markedly delayed the development of... 

Our finding of two pyrimidine biosynthetic enzymes (OMPDC and TS) in P. lophurae suggested that, unlike the duckling host, malaria parasites synthesized pyrimidines de novo from precursors such as C02, glutamine and aspartic acid (Walsh and Sherman, 1968b). Since that time, the enzymatic reactions of the de novo pyrimidine pathway and TS have been demonstrated in a variety of Plasmodium spp. and for P. falciparum (available online at http //sites.huji.ac.il/malaria/maps/pyrimidinemetpath. html last accessed 16 July 2008). 

In 1990, Schrevel et al. were able to record the presence of a variety of acid aspartic and cysteine proteases and metalloproteases, as well as alkaline proteases and aminopeptidases in the erythrocytic stages of a variety of Plasmodium spp. Unfortunately, since many of the enzymes catalogued were only partially purified, and sometimes appeared aggregated, their biochemical characteristics remain ill defined at best. More recent findings for plasmodial enzymes—principally cysteine, aspartic and metalloproteases—can be found in Rosenthal (2005) and in the Plasmodium database PlasmoDB (http //plasmodb.org) as well as in the website developed and curated by Hagai Ginsburg (http //sites.huji.ac.il/malaria). 

Plasmodium spp. to survive within the erythrocyte may also serve as rational drug targets (Vial and Calas, 2001 Vial and Ben Mamoun, 2005). 

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