Development Of New Antimalarial Drugs Research Articles

The malaria genome sequencing project.

An international consortium of genome centres, advanced development teams and funding agencies has begun the task of sequencing the genome of the parasite Plasmodium falciparum, the most important cause of human malaria. Sequencing is proceeding chromosome by chromosome, and the annotated sequence of chromosome 2 is nearly finished. With the continual release of sequence data as they are generated, malaria researchers have access to a steady stream of genomic sequences and will soon have the complete annotation of all of the estimated 5000-7000 P. falciparum genes. The task will then be how to best apply these data to the development of new anti-malarial drugs, vaccines and diagnostic tests. This review provides a brief overview of the Malaria Genome Sequencing Project and suggests potential directions for future malaria research.

Expression and properties of recombinant P. falciparum hypoxanthine-guanine phosphoribosyltransferase.

Plasmodium falciparum is the most deadly of the Plasmodium species causing human malaria. Due to the development of drug resistant strains of P falciparum, there is a need for the development of new antimalarial drugs.

30 years of science and technology: the example of malaria

In 1997 we celebrate the centenary of Ross’ discovery of the development of the malaria parasite in the mosquito. The next 30 or so years saw the laying down of a body of knowledge of the biology, immunology, and epidemiology of malaria that is surprisingly relevant today. The middle third of the century produced two powerful tools, chloroquine and DDT, and the belief that it would be possible at last to control malaria. In 1953 the World Health Assembly adopted a plan of eradication. There followed an extraordinary mobilisation of effort in many parts of the world and considerable initial success—but eradication was doomed to failure. The last third of Ross’ century began with the field crestfallen and uncertain, fixed in a mind set that still longed to eradicate malaria even when it was clear that this was impossible. Despite this unpromising start the next 30 years saw an explosion in technology and its application to malaria research.

In Vitro Antimalarial Activity of Vegetal Extracts Used in West African Traditional Medicine

Among strategies for the development of new antimalarials, a study of plants traditionally used in Africa against malaria has been pursued. Extracts obtained from the plants Azadirachta indica, Cinnamonum camphora, Lippia multiflora, Vernonia colorata, Guiera senegalensis, Combretum micranthum, and Ximenia americana, commonly used in Cote d'Ivoire by native healers for the treatment of malaria, were tested on two strains of Plasmodium falciparum: FcB1-Colombia (chloroquine-resistant) and F32-Tanzania (chloroquine-sensitive). Extracts were obtained after infusion and decoction, both techniques being used by most native healers. The antimalarial activities of the extracts were tested first by parasite 3H-hypoxanthine incorporation and second by visual evaluation of the activities of plant extracts on thin blood smears, which also permitted the determination of parasitic stages and parasite alteration. Among the seven plants tested, some had an apparent inhibitory effect on P. falciparum growth in vitro, while other seemed to be less efficient.

Mechanism-based development of new antimalarials: synthesis of derivatives of artemisinin attached to iron chelators.

Various derivatives of artemisinin covalently linked to iron chelators were synthesized, and their antimalarial activities were evaluated. Although results show no indication that the presence of an iron chelator in the vicinity of artemisinin potentiates its action, the linked compounds prepared still retain comparable activities to that of artemisinin.

Toxicity of adenosine analogues against human malaria (Plasmodium falciparum).

The transport and metabolism of purine nucleosides differ considerably between the human erythrocyte and the erythrocyte when infected with Plasmodium falciparum. 1-3. In addition, malarial parasites appear to be unable to synthesize their purines de novo and thus rely on salvage pathways to obtain preformed purines required for growth and division. Therefore, deprivation of essential purines by the blockage of purine salvage or metabolic pathways by various purine nucleoside analogues can lead to inhibition of parasite growth and the potential development of new antimalarials.

The Army's War against Malaria: Collaboration in Drug Research during World War II

During the second half of World War II, U.S. and Allied military and civilian scientists cooperated in helping the armed forces combat malaria. They worked through the Offices of the Surgeon General of the U.S. Army and the U.S. Navy, the National Research Council, the Board for the Coordination of Malarial Studies, the Office of Scientific Research and Development, the Australian Military Mission, and the British Medical Research Council, all in Washington, D.C. The Board for the Coordination of Malarial Studies, which the National Research Council established in November 1943 to guide research expansion and coordinate joint efforts, became the focal point for collaboration on research. These alliances produced hundreds of malaria studies and thousands of new compounds, some of which tested superior to traditional antimalarial drugs. This cooperative effort improved chemotherapy for the prevention and treatment of malaria after years of neglect in the development of antimalarial drugs. This article focuses on the establishment of the Board for the Coordination of Malarial Studies, the development of new antimalarial drugs, and collaboration with allies on drug research. The latter produced special U.S.-Australian and U.S.-Britain relationships.

Recent developments in 8-aminoquinoline antimalarials.

Malaria is an old scourge of mankind and mention of the disease is found in ancient writings in India, Egypt and China [1]. The clinical symptoms of this disease were described by Hippocrates 400 years before the Christian era [1]. Human population affected by malaria is alarmingly large in tropical regions although in the past the disease was also prevalent in temperate regions [1]. The respite from this disease after World War II, due to the success in the control of the vector mosquitoes and development of new antimalarials, was, however, short lived and malaria has staged a come back in recent years. Only two decades back WHO had stated The clinicians have at their disposal a complete series of effective drugs for the treatment of all stages of this disease’ [2] but in 1971 the same organization considered malaria eradication as a difficult problem both technically and politically [3] and commented ‘Thus there is no avoiding the conclusion that malaria will be with us for quite sometime. In order to cope more efficiently with this world-wide problem, much more research is required’ [4]. It would, therefore, be pertinent to analyse the main causes of this set-back. The principal reason is undoubtedly the appearance of drug-resistance in malarial parasites. Resistance to all the currently available drugs is a reality; even the age-old remedy, quinine, has the same limitations as the synthetic drugs.

Development of new antimalarial drugs.

SummaryStrains of Plasmodium falciparum that are resistant to chloroquine and to other widely-used synthetic antimalarial drugs have posed major difficulties in several parts of the world. Intensive efforts have been and are being made to develop new antimalarial agents that will be effective against such parasites. Several promising prospective new antimalarial agents have been identified and are now undergoing detailed clinical evaluation. The advent of one or two useful new agents should not serve as a source of renewed complacency. Parasites resistant to the latter agents may emerge and may limit their usefulness. Other new antimalarial drugs may be needed as backstops. There is and will be a continuing need to wage a strong investigative attack not only to develop new antimalarial drugs but also to develop other improved means with which to combat malaria.