From methylene blue to chloroquine: A brief review of the development of an antimalarial therapy

Department of Pathology, University of Minnesota School of Medicine, Duluth, MN, USA.
Parasitology Research (Impact Factor: 2.1). 03/2012; 111(1):1-6. DOI: 10.1007/s00436-012-2886-x
Source: PubMed


Malarial treatment is widely and readily available today. However, there was a time in the not-so-distant past when malaria was a deadly disease with no known cause or cure. In this article, we trace the origins of an antimalarial therapy from the discovery of the nature of the malarial parasite through the development of chloroquine. We dedicate this article to Johann "Hans" Andersag, the scientist who developed chloroquine, on the 110th anniversary of his birth, 16 February 1902.

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    • "Further, the synthesis of chloroquine by Hans Andersag in 1934 introduced a cheap antimalarial drug and a substitute for quinine. [5] Until the widespread resistance in 1960, quinoline-related antimalarial drugs played an important role in the treatment of malaria. Fortunately, in 1972, the Chinese discovered artemisinin from sweet wormwood plant Artemisia annua.[6] "
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    ABSTRACT: Malaria drug discovery is a challenging and difficult task due to the unavailability of the vaccine and lack of newer drugs. The most potent artemisinin and its deriva‐ tives, widely used in combination therapies for curing malaria worldwide are also now falling to resistance in some parts of the world. Thus, to combat malaria, new drugs possessing high therapeutic value, minimal toxicity, rapid efficacy and low cost are urgently needed. In this chapter, we will provide an integrated overview on the challenges and opportunities in malaria drug discovery with more emphasis on synthesis of peroxidic antimalarials.
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    • "Antimalarial medication, including chloroquine, has been the frontline choice in this battle. However, because of over-and inappropriate use, resistant strains of the malarial parasite started to evolve, diminishing the effects of the drug [6] [15]. Nevertheless, alternative uses of chloroquine include treatment of rheumatoid arthritis, discoid lupus erythematosus and amoebic hepatitis [5]. "
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    ABSTRACT: For many years chloroquine was used as a prophylactic agent against malaria, and more recently as a mild immunosuppressive. However, due to lengthy treatment periods, adverse effects have become apparent, which included retinopathy. The structurally related hydroxychloroquine is less toxic, thought to be owing to a lower tissue accumulation in melanin rich areas. This study primarily focused on quantifying melanin binding between chloroquine and hydroxychloroquine at physiological pH to investigate the potential link between binding and reported toxicity. In addition, for the first time this study quantified the actual extent of adsorption of chloroquine and hydroxychloroquine to melanin and examined the desorption profile of both drugs from melanin to demonstrate the affinity between the pigment and the solutes. The results suggest that there is a difference between the adsorption affinities of chloroquine and hydroxychloroquine, potentially explaining the differences in bioaccumulation in retinal tissue. In addition, both solutes displayed a strong physical attraction to the absorbent.
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    • "For many years it was the first-line antimalarial drug. However, as for many antimicrobial drugs, eventually (two decades later) drugresistant strains developed (Krafts et al. 2012). In the second half of the twentieth century, another important antimalarial drug was also developed in a time of war: mefloquine was number 142,490 of a total of 250,000 antimalarial compounds screened during the US Army's antimalarial drug discovery program. "
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