摘要
目的合成吲哚美辛5-氟尿嘧啶甲酯,并对其体内外抗肿瘤活性进行评价。方法以5-氟尿嘧啶及吲哚美辛为主要原料,经2步反应合成目标化合物。应用Hela、HT1080、kB、Heps及Bel-7 402等5种肿瘤细胞系对吲哚美辛5-氟尿嘧啶甲酯体外抗肿瘤活性进行评价;选用小鼠肉瘤S180瘤株、肝癌H22瘤株和Lewis肺癌实体瘤3种瘤株为指标,对吲哚美辛5-氟尿嘧啶甲酯的体内抑瘤活性进行考察。结果经熔点测定及1H-NMR、MS及IR确证目标产物结构,产品收率为66%;吲哚美辛5-氟尿嘧啶甲酯的体外抗肿瘤作用很弱,但对于小鼠S180、H22及Lewis 3种实体瘤的抑制作用与5-氟尿嘧啶相近。结论吲哚美辛5-氟尿嘧啶甲酯为5-氟尿嘧啶的前体药物。
Objective To prepare indomethacin 5-fluorouracil-1-ylmethyl ester and evaluated antitumor activity both in vitro and in vivo. Methods The target compound was synthesis by two steps with 5-fluorouracil and indomethacin as the starting materials. MTT assay was applied to study the anti-tumor effect of indomethacin 5-fluorouracil-1-ylmethyl ester on different tumor cell lines in vitro, at the same time, S180 sarcoma, H22 hepatoma and Lewis-transplanted mice were used to estimate the antitumor effect of indomethacin 5-fluorouracil-1-ylmethyl ester in vivo. Results The structure of indomethacin 5-fluorouracil-1-ylmethyl ester was confirmed by IR, ^1H-NMR and MS. The yield of indomethacin 5-fluorouracil-1-ylmethyl ester was 66%. Inhibitory effect of indomethacin 5-fluorouracil-1-ylmethyl ester was poorer than 5-fluorouracil in vitro. The inhibitory ratio of indomethacin 5-fluorouracil-1-ylmethyl ester was comparable to 5- fluorouracil in vivo. Conclusions Indomethacin 5-fluorouracil-1-ylmethyl ester is a promising prodrug of 5- fluorouracil.
出处
《沈阳药科大学学报》
CAS
CSCD
北大核心
2007年第11期687-690,699,共5页
Journal of Shenyang Pharmaceutical University
