A new series of mono-and di-hydroxy substituted naphthalene compounds was synthesized and found to possess antimalarial activity against P. gallinaceum infection of young chicks. A representative compound with a high degree of activity was chosen for extensive testing against other malarial species and for pharmacological investigation. The formula of this compound, number 377C54, was 1: 6-dihydroxy-2: 5-bis(cyclohexylaminomethyl)naphthalene dihydrochloride. Effective doses against P. gaifinaceum in chicks, P. berghei in mice and P. cathemerium in canaries were 2.3, 4.0, and about 6 mg./kg. respectively. Compound 377C54 acted rapidly against the parasitaemia of P. gallinaceum in chicks and P. knowlesi in a rhesus monkey. Parasiticidal activity remained in the blood of chicks for a long time after a single oral dose. The drug can be estimated by the production of colour on coupling with diazotized p-nitroaniline. Drug concentrations in blood from chicks and humans rose rapidly after oral administration. In tissues from chicks, particularly liver and lung, the drug persisted for a long period. An unsuccessful attempt was made to induce resistance to 377C54 in a strain of P. gaifinaceum. Extensive pharmacological investigation showed that 377C54 possessed no special pharmacological properties. Several derivatives of 1-and 2-naphthol were tested for antimalarial activity in the American wartime screening programme (Wiselogle, 1946). One member of the series, which showed activity against laboratory malaria infections, SN 6520 [2-(dimethylaminomethyl)-1-naphthol], was given clinical trial against blood-induced Plasmodium vivax infections. It was found to be inactive at doses of 2 g. daily. No tests were made for either prophylactic or curative activity.The experiments recorded here are the result of the observation that 1-cyclohexylaminomethyl-2-naphthol (371C52) showed antimalarial activity against blood-induced P. gallinaceum infection in young chicks. METHODS The compounds were made by the method described by Burke, Kolbezen, and Stephens (1952 Screening and assaying of new compounds were carried out using P. gallinaceum infections of 5-or 12-day-old chicks. The methods used were those previously described by Falco, Goodwin, Hitchings, Rollo, and Russell (1951). Where compounds were also tested against P. berghei in mice the technique of the same authors was used. Where only a screening test was carried out the compound was awarded a "score" according to the following key: 0=No activity at 100 mg./kg. 1 = Slight activity at 100 mg./kg.2=Active at doses between 100 and 10 mg./kg. A dose was considered to be "active" when the mean % parasitaemia of the treated group of animals was lowered to 1 % or less of the mean % parasitaemia of untreated controls. When an assay was carried out, the median effective dose (ED50) was determined. This is defined as the dose which reduces parasitaemia to 50% of the mean parasitaemia of untreated controls. A 3-or 4-dose assay was used as described by Rollo (1952).Compound 377C54 was ...

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Early types of antibacterial substances were not specifically antibacterial, but were usually toxic to all living cells, and were of value only in so far as they could be employed without serious damage to the host. The search for more suitable antibacterial agents resulted in the preparation and testing of many substances of widely different constitution, and it was from the empirical yet systematic investigations of one such class of chrysoidine dyestuff that knowledge of the activity of sulphanilamide arose. The growing evidence that the antibacterial action of sulphanilyl drugs was due to competition with an enzymic metabolic process suggested to Fildes [1940] a new approach to the problem. This was the design of antibacterial agents by the synthesis of compounds with a close spatial resemblance to substances vital to, or closely associated with, bacterial growth and reproduction. These growth substances include the water-soluble vitamins of the animal world, which now appear to be essential to the life of all growing cells. The method has been recently used in a sufficiently diverse series of independent investigations to confirm the principle [Mcflwain, 1943]. Other compounds which exert a pronounced physiological activity in minute concentration are the animal hormones related to cyclopentanophenanthrene; for example, oestradiol, when injected into an ovariectomized rat of 50 g. body weight in a dose of 02 jig., is capable of doubling the weight of the uterus; with a blood volume of 2 ml., this represents an activity at a concentration of 1 in 107. These compounds are not known to be hormones for the vegetable kingdom, but they are widely distributed in nature and are probably constituents of all growing cells, being found in all plants and bacteria [Aschheimn & Hohlweg, 1933], as well as in all animals. It seems to us that these compounds can readily be incorporated into the living cell, and that such molecules constitute suitable material

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