Plasmodium berghei

Peeters, P. A. M., Brunink, B. G., Eling, W. M. C., and Crommelin, D. J. A. (1989). Therapeutic effect of chloroquirie (CQ) containing immunoliposomes in rats infected with Plasmodium berghei parasitized mouse red blood cells comparison with combinations of antibodies and CQ or liposomal CQ, Biochim. Biophys Acta, 981, 269-276. 

An extensive series of thiosemicarbazones obtained from 2-acetylpyridine was tested by Klayman et al. [4, 85] for antimalarial activity against Plasmodium berghei in mice. The molecular features essential for activity were found to be a 2-pyridylethylidene moiety, the presence of the thiocarbonyl sulfur, and certain, bulky or cyclic substituents at the terminal AT-atom. The most active 2-acetylpyridine thiosemicarbazones were " N-phenyl- and those with azacycUc substituents. For example, iV-substituents of 4-methylpiperidine, piperazine, and azabicyclo[3.2.2.]nonyl-, 4, were curative at a dose level as low as 20 mg/kg. 

Singh, R P. et al., Immunomodulation by morphine in Plasmodium berghei-infected mice, Life Set, 54, 331, 1994. 

The immune system of the mouse may also be susceptible to the effects of acute oral exposures to di-/ -octylphthalate (Dogra et al. 1989). Three-month-old Swiss albino mice were exposed to di-n-octylphthalate by gavage for 5 days at 0, 650, or 2,600 mg/kg/day (acute LD50 was 13,000 mg/kg). Mice were subsequently exposed by intraperitoneal injection to either encephalomyocarditis virus or the malarial protozoan, Plasmodium berghei. Maximum mortality levels were reached 8-10 days after viral infection and were 20% (0 mg/kg/day), 40% (650 mg/kg/day), and 70% (2,600 mg/kg/day). Malarial lethality reached plateau levels 4-11 days postinfection of approximately 20% (0 mg/kg/day), 25% (650 mg/kg/day), and 70% (2,600 mg/kg/day), then increased to 55%, 70%, and 85%, respectively, by postinfection day 19. Respective mean survival times were calculated to be 13.50, 12.15, and 6.25 days. During the first 14 days after protozoal infection, the percentage of mouse erythrocytes infected with the parasite in the high-dose... 

Apicomplexan parasites cause life threatening diseases like malaria, cryptosporid-iosis, toxoplasmosis, coccidiosis. Suberic acid bisdimethylamide which also inhibits HDA selechvely arrests tumor cells as opposed to normal mammalian cells, has an in vivo cytostatic effect against the acute murine malaria Plasmodium berghei (Andrews et al, 2000). 

Simtharasamai, P., and Marsden, P. D., Studies of splenomegaly in rodent malaria. Ill Protein-calorie malnutrition and splenomegaly in mice infected with Plasmodium berghei yoeii. Trans. Roy. Soc. Trop. Med. Hyg. 66, 214-221 (1972). 

Other synthetic candidates worthy of mention inclnde the C3 aryl trioxanes (75a and 75b) " and the endoperoxide analogue (76) ". These latter compounds have oral activity (ED50) as low as 0.5 mgkg in mice infected with Plasmodium berghei. 

In vivo assays were performed using the standard Peters 4-day test. Ihe activity refers to oral antimalarial activity and reflects the concentration of drug required to reduce parasitaemia, in mice infected with Plasmodium berghei, by 50% of the control. 

Kd-restricted plasmodium berghei circumsporozoite peptide (253-260) JVct-[Bz(2-OH,3-125I,4-N3)]-Tyr-Ile-Pro-Ser-Ala-Glu-Lys(jVe-bio- post-SPPS with Bz(2-OH,3-I,4-N3)-OSu [401... 

Wysor MS. 1975. Orally administered silver sulfadiazine Chemotherapy and toxicology in CF-1 mice Plasmodium berghei (malaria) and Pseudomonas aerygubis. Chemotherapy 21 302-310. 

Takeuchi (6) demonstrated that the tetronic acid-containing antibiotic, (V), was effective in the treatment of antiprotozoal infections including Plasmodium berghei. 

The interaction of ellipticine derivatives with topoisomerase II enzymes in Plasmodium berghei (163), a parasite of mouse red blood cells, mouse lymphoma L5178Y cells (164), simian virus 40 CV-1 cells (165), Trypanosoma cruzi (166,167), and the human small-cell lung cancer cell line NCI N417 (168,169) has been studied. In the latter study, the highest in vitro activity in the topoisomerase II-DNA cleavage reaction and decatenation was observed for elliptinium (5) and datelliptium (384) (769). 

All three Artemisia derivatives are quickly hydrolysed to the active substance dihydroartemisinin. They produce a more rapid clinical and parasitological response than other antimalarial drugs. There are no reports of significant toxicity, and as late as 1994 there was no convincing evidence of specific resistance, but chloroquine-resistant Plasmodium berghei is resistant to artemisinin as well. The recrudescence rate is fairly high (1). 

Ndifor AM, Howells RE, Bray PG, Ngu JL, Ward SA. Enhancement of drug susceptibihty in Plasmodium falciparum in vitro and Plasmodium berghei in vivo by mixed-function oxidase inhibitors. Antimicrob Agents Chemother 1993 37(6) 1318-23. 

The chemotherapeutic response of Plasmodium berghei to various combinations of mefloquine with other drugs (sulfadoxine + pyrimethamine, primaquine, floxacrine) have shown that the desired effects are purely additive (SEDA-13, 809), so the adverse effects too are probably only those of the individual compounds. Adverse reactions occurred in 46% of 400 patients treated with Fanimef (mefloquine + pyrimethamine + sulfadoxine) (SEDA-12, 693). Of note were dizziness (29%), nausea (9.5%), vomiting (7.3%), weakness/lassitude (5.8%), abdominal discomfort or pain (5.5%), diarrhea (3.8%), pruritus (3.0%), insomnia (2.0%), and headache (2.0%). 

Aplasmomycin inhibits Gram-positive bacteria including mycobacteria in vitro, see also Table 5. Male mice were infected intraperitoneally by Plasmodium berghei and when aplasmomycin in peanut-oil was administered orally, the number of plasmodium-containing red cells decreased and all treated mice survived. It was on the basis of this potent antiplasmodium activity that aplasmomycin received its name. The acute toxicity in mice was 125 mg/kg by intraperitoneal injection. 

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