STUDIES ON ANTITUBERCULOUS ACTIVITY OFα- ETHYL-THIOISONICOTINAMIDE-SULPHOXIDE
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Kane, Bieder and coworkers formerly reported on α-ethyl-thioisonicotinamide-sulphoxide (Th-sulphoxide) as a metabolite of 1314 Th, and in the previous paper we also published on its chemical natures and polarographic behaviors by using the material synthesized by Prof. Taniyama.<BR>The present paper deals with an experiment conducted for the purpose of investigating the effect of Th-sulphoxide on the tubercle bacilli in vitro, and its toxicity in vivo.<BR>1) Toxicity of Th-sulphoxide The toxicity of Th-sulphoxide in mice (17g of weight) was so slight that LD<SUB>50</SUB> was between 750mg/kg and 1, 000mg/kg by intraperitoneal injection, and above 1, 000mg/kg oral abmini stration (Table 1 a, b).<BR>2) Antituberculous effect of Th-sulphoxide<BR>a. The effect in Ogawa's egg media by vertical diffusion method.<BR>The length of growth inhibitory area for each concentration of Th-sulphoxide was longer than that of 1314 Th (Table 2). For example, in 1γ/0.5ml concentration of the drug, the length of inhibitory zone of Th-sulphoxide was 7.3-9.6mm, while that of 1314Th was 5.4mm, indicating that water soluble Th-sulphoxide is much more diffusible than water insoluble 1314Th.<BR>b. The effect in liquid culture media and in 1% Ogawa's egg media.<BR>Both in the Kirchner-albumin medium and Dubos-albumin liquid one, the minimal growth inhibitory concentration of Th-sulphoxide was 2.5-5.0γ/ml, revealing almost the same grade of antituberculous activity as that of 1314Th. However in 1% Ogawa's egg medium the minimal inhibitory concentration of the drug was 10-25γA/ml (Table 4 a, b), showing that the inhibitory effect of Th-sulphoxide is far smaller in the Ogawa's egg medium than in the liquid medium. Since Th-sulphoxide is unstable to heating, the above difference in the antituberculous activity between both media may be partly due to the effect of heating.<BR>3) Antituberculous activity of the serum of rabbit intraperitoneally injected with Thsulphoxide<BR>Rabbits were injected intraperitoneally with 300mg of Th-sulphoxide and at intervals of 30, 60, 120 and 240 minutes, their blood was taken. The antituberculous activity of these sera was examined by the vertical diff usion method (Table 6). The growth inhibitory activity of the serum was highest 30 minutes after the injection and after 240 minutes there was not observed any activity, showing that the absorption and excretion of Th-sulphoxide in vivo is relatively rapid.
- 一般社団法人 日本結核病学会の論文
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