Chloroquine discovery

Nalidixic acid, the prototype of this family of drugs, was synthesized as the result of the discovery that an impurity, isolated during the preparation of the antimalarial chloroquine, had significant antibacterial activity. It was... 

Fluoroquinolones The story of fluoroquinolones began in the 1950s with the discovery of the antibacterial properties of 7-chloroquinolone, a side product of the preparation of chloroquin and glafenin. Further research led to the... 

Following this line of work, we made the discoveries reported here. Before we indicate these, we note that the microarray datasets that we analyzed for tetracycline and chloroquine do not contain many differentially regulated reactions. The possibility remains that studying drug resistance mechanisms of the malaria parasites at the transcriptional level of their proteins is not reliable (Karine Le Roch, personal communication). 

Quinine (5) isolated from Cinchona bark was one of the hrst antimalarials discovered, and it became a model for the discovery and development of some of the most successful anti-malarial agents, chloroquine and its successors. However, the... 

In a further effort to develop better antimalarials by changing the substitution at the 4-amino function of chloroquine led to the discovery of hydroxychloroquine (5) with high antimalarial activity [11,12]. The search for newer 4-aminoquinoline drugs received a new dimension when Burckhalter et al. [13] discovered the antimalarial activity with some a-dialkylamino-o-cresols of the type 6 and 7. Consequently these authors prepared a large variety of Mannich bases attached to the 7-chloroquinolin-4-... 

Up to the middle of this century quinine (1) was used for the treatment of malaria, and with the widespread development of chloroquine-resistant strains of Plasmodium falciparum it has become important again. Quinine has been used for the treatment of malaria for more than 350 years and has its origin in Peru in the early 17th century. Quinine was the lead structure in the discovery of new synthetic derivatives like mefloquine that have higher antimalarial activity. This section will focus on other new quinoline alkaloids. The mechanism of antiplasmodial action and resistance of quinolines is well described elsewhere [116]. 

Dissatisfaction with the performance of pamaquine as a synthetic substitute for quinine led to further synthetic work in the acridine series, and ultimately to the discovery of the antimalarial properties of quinacrine (Atebrin, Mepacrine, 12). Other acridines to find clinical use are acriquine (13), aminoacrichin (14), and azacrin (15), the latter being designed to combine the features of a 4-aminoquinoline and an 8-aminoquinoline. Quinacrine was much less active than pamaquine in early tests against avian malaria, but it was four times as potent against P. berghei in mice [79], It was widely used to treat Allied troops during World War II, but has now been wholly superseded by other compounds such as chloroquine. Nevertheless, it is... 

Acridines were also found to have potent activity against malaria. This discovery was driven by the limited availability of Quinine during World War II and quinacrine became the main malarial treatment in both England and the United States. The development work done with quinacrine lead directly to the development of chloroquine, one of the most successful treatments for malaria. 

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