以氨基酸为载体的亚硝脲类化合物的合成及其抗肿瘤活性

SYNTHESIS AND ANTITUMOR ACTIVITIES OF NITROSOUREAS WITH AMINO ACID ESTER AS CARRIERS

合成了16个以氨基酸为载体的亚硝脲类化合物。初步药理试验表明,其中苯甘氨酸酯氯乙亚硝脲(Ⅱ)和苯丙氨酸酯氯乙亚硝脲(Ⅱ_7),在剂量为27mg/kg 时对肉瘤 S37的抑制率分别为79.7和79.8%。剂量为63mg/kg 时,对大鼠 Walker 256癌肉瘤的抑制率,Ⅱ_5为98.5,Ⅱ_7为99%。Ⅱ_5和Ⅱ_7对小鼠 S37的化疗指数分别为7.66和10.33。

Sixteen new nitrosoureas with amino acid esters,e.g.,glycine,alanine,phenylglycine,phenylalanine,methionine as carriers were synthesized.In vivo test in mice beaching,sarcoma 37,phenylglycine nitrosourea(Ⅱ_5)andphenylalanine nitrosourea(Ⅱ_7)ip 27 mg/kg possessed rate of inhibition 79.7and 79.8%,respectively,In rats bearing Walker carcinosarcoma 256,Ⅱ_5 andⅡ_7 ip 63 mg/kg possessed rate of inhibition 98.5 and 99%,The chemotherapeu-tic index of Ⅱ_5 and Ⅱ_7 was 7.66 and 10.33,respectively.