Against Plasmodium

It should be noted that dmgs may operate by more than one mechanism, and may possess a specific mode of action against one species of plasmodium but lack efficacy against others. In addition, antimalarial dmgs may be classified according to their stmctural types. 

Several 2,3-disubstituted-4(3/f)quinazolinones were active against Plasmodium gallinaceum and showed antiinflammatory action on experimental edemas in animals. 6-(m-Amidinophenyldiazoamino)-... 

Although a humoral immune response is the primaiy protection against most viral and some bacterial diseases, protective defense against other pathogens such as HIV, Plasmodium and Mycobacterium tuberculosis requires a cytotoxic response mediated by CD8+ T-cells (CTL response). Since the introduction of the vaccination concept by Jenner almost 200 yeats ago, only few vaccines have been developed that are able to induce a CTL response. These vaccines are usually attenuated live vaccines that are accompanied by certain risks and are not readily available for most pathogens. The immense appeal of DNA vaccines can be attributed to a considerable part to the fact that they are able to induce... 

Antimalarial dragp interfere with, or are active against, die life cycle of die plasmodium, primarily when it is present in the red blood cells. Destruction at this stage of die plasmodium life cycle prevents die development of die male and female forms of the plasmodium. This in turn keeps die mosquito (when die mosquito bites an infected individual) from ingesting the male and female forms of the plasmodium, thus effectively ending die plasmodium life cycle (Pig. 16-1). 

Bfx and Fx derivatives have been evaluated against the parasites Trypanosoma cruzi (T. cruzi), which is responsible for American Trypanosomiasis and Plasmodium falciparum (P. falciparum) responsible for Malaria. 

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. 

Baird et al. [154] reported that primaquine base (30 mg/day) had protective efficacy against Plasmodium falciparum and P. vivax of 85-93%. Among 339... 

Titanium tetrachloride-catalysed Michael additions of trimethylsilyl enol ethers to artemisitene afforded a neat route to 14-substituted artemisinin derivatives of type 125 (eg. R = allyl) and to 9-epiartemisinin derivatives 126 some of these compounds were more active against Plasmodium falciparum than artemisinin <00BMCL1601>. A series of 11-azaartemisinins also have better activity than artemisinin <00BMC1111>. On the other hand, epiartemisinin, prepared by base-catalysed epimerisation of artemisinin, has been shown to have poor antimalarial activity <00HCA1239>. 

Deoxoartemisinin and carboxypropyldeoxoartimisinin have also been shown to have anti-tumour activity and, NMR studies on solution conformations have been reported <00BBR359>. One of the problems with artemisinin use is its poor water solubility characteristics. An attempt to rectify this, and to overcome stability problems associated with sodium artesunate in solution, has involved the introduction of amino group functionality as in 127 (eg. R = 0(CH2)3NR r2 where NR r2 = morpholine). The maleate salt of this compound has reasonable water solubility and aqueous solutions are stable at room temperature for an extended time. However activity against Plasmodium knowlesi in rhesus monkeys after oral administration was poorer compared with artesunic acid <00JMC1635>. 

A successful human trial of alum-adsorbed liposomes containing monophospho-ryl lipid A recently demonstrated that a formulation consisting of a combination of oil/water and adsorbent adjuvants can have considerable safety and efficacy and may be useful in the development of a potential vaccine against Plasmodium falciparum [29],... 

A8. Alving, A. S., Johnson, C. F., Tarlov, A. R., Brewer, G. J., Kellermeyer, R. W., and Carson, P. E., Mitigation of the hemolytic effect of primaquine and enhancement of its action against exoerythrocytic forms of the Chesson strain of Plasmodium vivax by intermittent regimens of drug administration. Bull. World Health Organization 22, 621-631 (1960). 

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). 

Very recently elisapterosin A (30) [18, 19] was found to exhibit strong antiplasmodial activity (IC5010 pg/ml) against Plasmodium falciparum, the parasite responsible for the most severe forms of malaria. 

Artemisinin, a tetracyclic 1,2,4-trioxane isolated from Artemisia annua L., is currently recommended as a first-line agent against Plasmodium falciparum malaria. Artemisinin and its synthetic derivatives have also been shown to be promising prototypes for the development of new antiproliferative agents. This chapter presents the recent advances on the analytic methods for extraction and quantification of artemisinin from A. annua plants as well as the biological properties of this natural product. 

Barfod A, Persson T, Lindh J (2009) In vitro selection of RNA aptamers against a conserved region of the Plasmodium falciparum erythrocyte membrane protein. Parasitol Res 105 1557-1566... 

Examples of fluorine-containing imino sugars as partial structures of PNPs have been reported. The S -deoxy-S -fluoro compound 116 ( S -F-Imucillin H, Scheme 29) was found to be a nanomolar inhibitor of human PNP (1 nM) as well as that of Plasmodium falciparum (A) 60 nM).237 2,-Deoxy-2,2 -difluoro derivative 117 ( -diF-immucillin-H ) exhibited slightly more inhibitory power against the microbial enzyme and an enhanced selectivity of more than three orders of magnitude (ATj 1.4 nM vs. 15 pM).238 Another type of inhibitor, the 3-fluoro compound 118 ( F-DADMe-immucillin-H ) was shown a potent picomolar inhibitor of the human enzyme (Kf 32 pM), with some selectivity over the Plasmodium phos-phorylase (2.6 nM), whereas the enantiomer 119 was 50- to 100-fold less active 239,240... 

Similar synthetic vaccines have also been constructed which confer immunological protection against bacterial toxins, including diphtheria and cholera toxins. While coupling to a carrier is generally required to elicit an immunological response, some carriers are inappropriate due to their ability to elicit a hypersensitive reaction, particularly when repeat injections are undertaken. Such difficulties can be avoided by judicious choice of carrier. Often a carrier normally used for vaccination is itself used, e.g. tetanus toxoid has been used as a carrier for peptides derived from influenza haemagglutinin and Plasmodium falciparum. 

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