三氮脒与含苯磺酰胺结构单元的新型三氮脒衍生物对小鼠急性毒性试验

Acute toxicity test of diminazene and novel diminazene derivatives containing sulfonamide moiety in mice

为了比较三氮脒及含苯磺酰胺结构单元的新型三氮脒衍生物在不同给药方式下对小鼠的毒性,以评估两种药物的安全性,根据改良寇氏法测定三氮脒及三氮脒衍生物在不同给药方式下对小鼠的半数致死量(LD_(50))及95%的可信限,给药方式分为腹腔注射和皮下注射两种。试验结果显示,腹腔注射时三氮脒和新型衍生物的LD_(50)分别为235.0 mg/kg、251.8 mg/kg,95%可信限为157.0～351.7 mg/kg、168.6～376.0 mg/kg;皮下注射时三氮脒的LD_(50)为257.6 mg/kg,95%可信限为171.2～387.8 mg/kg,新型衍生物的LD_(50)>500.0 mg/kg。以上试验结果表明,新合成的衍生物其毒性和三氮脒相比,仅皮下注射时LD_(50)显著降低。对含苯磺酰胺结构单元的新型三氮脒衍生物的研发将具有重要的意义。

To compare the toxicity of diminazene and novel diminazene derivatives containing sulfonamide moiety in mice in different methods of administration and assess the safety of the two drugsfurther, we used the modified Karber's methodwas to determine the LD50 and 95% confidence interval of the diminazene and novel diminazene derivatives in mice. Intraperitoneal injection and subcutaneous injection were used. The results showed that the LD50 of diminazene and novel diminazene derivatives through intraperitoneal injection were respectively 235. 0 mg/ kg, 251. 8 mg/ kg, respectiveliy The 95% confidence interval were 157. 0 ~ 351. 7 mg/ kg, 168. 6 ~376. 0 mg/ kg, respectivelip. The LD50 of diminazene and novel diminazene derivatives through subcutaneous injection were respectively 257. 6 mg/ kg and above 500. 0 mg/ kg, respectiveliy, The 95% confidence interval of diminazene was 171. 2 ~ 387. 8 mg/ kg. Experiments showed that the new synthetic derivatives were significantly less toxic than diminazene. The study will provide important guiding significancefor the development of novel diminazene derivatives containing sulfonamide moiety.