Malaria evaluation

The best example of the class of phenanthrene-methanols is halofantrine (66, Halfan [36167-63-2]) a dmg that is effective against chloroquine-resistant malaria and is now being evaluated in Africa. It produces temporary gastrointestinal disturbances. 

A large and rapidly growing number of clinical trials (phase I and phase II) evaluating the potential of DNA vaccines to treat and prevent a variety of human diseases are currently being performed ( http // clinicaltrials.gov) however, there is yet no licensed DNA vaccine product available for use in humans. The clinical trials include the treatment of various types of cancers (e.g., melanoma, breast, renal, lymphoma, prostate, and pancreas) and also the prevention and therapy of infectious diseases (e.g., HIV/ABDS, malaria, Hepatitis B vims, Influenza vims, and Dengue vims). So far, no principally adverse effects have been reported from these trials. The main challenge for the development of DNA vaccines for use in humans is to improve the rather weak potency. DNA vaccines are already commercially available for veterinary medicine for prevention of West Nile Vims infections in horses and Infectious Hematopoetic Necrosis Vims in Salmon. 

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. 

Libraries of hundreds to thousands of spatially separate inhibitors have been prepared and screened to identify small molecule inhibitors of the human protease cathepsin D and the essential malarial proteases, plasmepsins I and II. The best inhibitors do not incorporate any amino adds and possess high affinity (Kj<5 nM).1241 Furthermore, these lead compounds were optimized by combinatorial methods for good physicochemical properties and minimal binding to human serum albumin. The optimized inhibitors effectively block cathepsin D-mediated proteolysis in human hippocampyl slices and are currently being used to evaluate the therapeutic potential of cathepsin D inhibition in the treatment of Alzheimer s disease. Additionally, the plasmepsin inhibitors serve as promising leads for the treatment of malaria. 

FDA) for use in humans to treat malaria because this drug is considered a safe drug with few side effects.These features prompted various scientists around the world to evaluate the potential of artemisinin (1) and derivatives to control cancer cells proliferation. This chapter reviews the recent advances on analytical methods for extraction and quantification of artemisinin (1) from A. annua. Examples of artemisinin-derivatives with antiproliferative activities are listed, describing the structure-activity relationships of 96 compounds. This knowledge is essential for future development and use of artemisinin derivatives in cancer therapy. The mechanism of action of artemisinin and derivatives on cancer cells have been well reviewed in literature and therefore is not discussed in this chapter. 

Chadwick J, Mercer AE, Park BK, Cosstick R, O Neill PM. (2009) Synthesis and biological evaluation of extraordinarily potent C-10 carba artemisinin dimers against P. falciparum malaria parasites and HL-60 cancer cells. Bioorg Med Chem 17 1325-1338. 

Pichyangkul, S., Gettayacamin, M., Miller, R.S., Lyon, J.A., Angov, E., Tongtawe, P., Ruble, D.L., Heppner, D.G., Jr., Kester, K.E., Ballou, W.R., Diggs, C.L., Voss, G., Cohen, J.D., Walsh, D.S. Pre-clinical evaluation of the malaria vaccine candidate P. falciparum MSPI42 formulated with novel adjuvants or with alum. Vaccine 22 (2004) 3831-3840. 

A number of DNA vaccines have progressed into clinical trials for the prevention and/or treatment of HIV, malaria, cytomegalovirus (CMV) and hepatitis B and C [23,24], So far the DNA vaccines have been well tolerated in clinical trials [23] and have produced both humoral and cellular responses in some trials [41], but overall the potency has been disappointing [20], Although DNA is typically injected intramuscularly, alternative delivery systems have been evaluated. One such system that has been tested clinically for hepatitis B involves coating plasmid DNA onto gold beads, which are then propelled into the epidermis using a needle-free delivery system [20,42,43],... 

Since the Expert Committee last considered the chemistry and specifications of pesticides in 1989, 12 pesticide products have been fully evaluated for vector control, mainly for indoor residual spraying and insecticide treatment of mosquito nets for malaria vector control WHO specifications have been published for these products. 

Every country in Latin America and the Caribbean has at some time developed a national malaria control programme. In the past, these programmes were responsible for applying most of the insecticides used in public health. However, conventional indoor residual applications have now declined. Insecticide-treated mosquito nets have been used to a limited extent and several countries have used space spray applications as an alternative or supplement to residual applications. In southern Mexico, low-volume residual application of insecticides using motorized back-pack UL sprayers has been evaluated for malaria and dengue control. 

Malaria remains one of the most important diseases of humanity with over half of the world population at risk of infection. It affects mainly those living in tropical and subtropical areas with an incidence of 500 million cases per year globally. The antimalarial activity of 4-(5-trifluoromethyl-17/-pyrazol-l-yl)chloroquine analogues 875 has been evaluated in vitro against a chloroquine-resistant Plasmodium falciparum clone <2006BML649>. 

A number of histidine analogues, including 2-azido-L-histidine (201), have been evaluated by the NIH as part of a programme directed towards the development of new antimalarials for the prophylaxis and treatment of drug-resistant Plasmodium falciparum malaria [261]. Asexual P. falciparum parasites have a much higher histidine content than mammalian cells, and several histidine-rich proteins are thought to be functionally important in... 

Artemisinin derivatives (artesunate and artemether) for the treatment of multidrug-resistant Plasmodium falciparum malaria have been evaluated in 83 Karen pregnant women in Thailand 55 women were treated for recrudescent infection after quinine or mefloquine, 12 for uncomplicated hyperparasitemic episodes, and 16 had not declared their pregnancy when treated (32). 

Van Vugt M, Angus BJ, Price RN, Mann C, Simpson JA, Poletto C, Htoo SE, Looareesuwan S, White NJ, Nosten F. A case-control auditory evaluation of patients treated with artemisinin derivatives for multidrug-resistant Plasmodium falciparum malaria. Am J Trop Med Hyg 2000 62(l) 65-9. 

Isolated thrombocytopenia after the use of quinine for malaria or leg cramps has been described in isolated cases. The FDA s Center for Drug Evaluation and Research received 141 reports of isolated thrombocytopenia in association with quinine from 1974 to December 2000 (18). After elimination of cases that were confounded by acute or chronic disease or concomitant drug therapy, 64 reports of quinine-associated thrombocytopenia were analysed. Thrombocytopenia occurred soon after the start of therapy (median 7 days) and was often severe (hospitalization reported in 55 of the 64 cases). 

---