摘要
目的首次合成未见报道的N,N-二(2-氯乙基)芥酸酰胺,探讨其体内外抗肿瘤活性。方法①以芥酸和双(2-氯乙基)胺盐酸盐为原料、吡啶为催化剂合成N,N-二(2-氯乙基)芥酸酰胺,分离纯化后核磁共振谱确证结构;②用N,N-二(2-氯乙基)芥酸酰胺作用于Tca8113,用倒置显微镜镜下观察其对Tca8113细胞的生长状况的影响,PI染色经流式细胞术分析其杀伤效应;③S180小鼠动物肿瘤模型观察N,N-二(2-氯乙基)芥酸酰胺对肿瘤的体内抑制作用。结果合成出了N,N-二(2-氯乙基)芥酸酰胺并确证了其结构;N,N-二(2-氯乙基)芥酸酰胺于体外0.15～10.0μg/ml的浓度范围对Tca8113有较强的杀伤效应,杀伤率均超过30%,但与浓度递增无明显的正相关,在100.0μg/ml以上的浓度反而杀伤效果不佳;体内抑制S180的生长,剂量为5mg/kg时,抑制作用最好,生命延长率为38.20%,体重平均增长速率为2.45%。结论采用微型合成法能够快速、方便地合成出N,N-二(2-氯乙基)芥酸酰胺;N,N-二(2-氯乙基)芥酸酰胺在在体内外具有明显的抗肿瘤活性。
Objective To study the synthesis of the N,N-di（2-chloroethyl）erucamide and its activity of anti-tumor in vitro and vivo.Methods①Through the micro-organic synthesis technology,erucic acid was coupled with N,N-di（2-chloroethyl）amine hydro-chloride as starting materials,pyridine as catalyst to synthesize the N,N-di（2-chloroethyl）erucamide.Isolation and purification were achieved by silical gel column chromatography,and its structure was confirmed by nuclear magnetic resonance spectrum.②Tca8113 was cultured in media with N,N-di（2-chloroethyl）erucamide,and the cell growth was observed through inverted microscope.The anti-tumor effect was detected by flow cytometry.③Investigate the growth inhibitory for murine tumormodels in vivo.ResultsThe N,N-di（2-chloroethyl）erucamide was synthesized successfully and its strong killing effect was recorded within 0.15μg/ml^10.0μg/ml in vitro,and the rate was beyond 30%,but the effect had no positive correlation with concentration.The inhibitory concentration 50 %（IC50）was 0.135 38μg/ml.This compound had significant inhibitory effect on S180 growth in vivo.As dose was 5mg/kg,the inhibitory effect was the best,the life-prolonging rate was 38.20%,the average growth rate of body weight was 2.45%.ConclusionThrough the microscale organic synthesis,N,N-di（2-chloroethyl）erucamide can be synthesized quickly and conveniently.N,N-di（2-chloroethyl）erucamide has obvious anti-tumor effect in vitro and in vivo.
出处
《时珍国医国药》
CAS
CSCD
北大核心
2010年第9期2162-2164,共3页
Lishizhen Medicine and Materia Medica Research
基金
国家自然科学基金(No.30560186)
广西科技厅广西科学基金项目(No.0728128)
广西科技厅广西科学基金项目(No.0991147)
