两个Galaxamide类似物的固相合成及抗肿瘤活性研究  

Study on Solid Phase Synthesis and Anti-Tumor of Two Galaxamide Analogues

作　　者：钟生辉[1] 白德发[1] 陈建维[1] 聂伟恒 徐石海[1] 

机构地区：[1]暨南大学生命科学技术学院化学系,广东广州510632

出　　处：《精细化工》2016年第8期903-908,共6页Fine Chemicals

基　　金：国家自然科学基金(21172094;41376155;21372100;U1301131);广州市科技项目(2013000000163);国家高技术研究发展计划(863计划)(2013AA092902)~~

摘　　要：以N-芴甲氧羰基-L-亮氨酸(Fmoc-Leu-OH)和N-芴甲氧羰基脯氨酸(Fmoc-Pro-OH)为原料,采用经典的Fmoc固相合成法,通过对氨基酸N端的保护及脱保护、氨基酸的甲基化、缩合等步骤合成线性五肽,以缩合试剂六氟磷酸苯并三唑-1-基氧基三吡咯烷基磷(Py \BOP)关环,分别以59.5%和41.1%的环合收率得到了两个新的环五肽化合物G_1和G_2,结构通过~1HNMR、^(13)CNMR、ESI-MS进行确认。采用MTT法对目标化合物G_1和G_2进行了体外抗肿瘤活性的研究。结果表明:含有脯氨酸片段的Galaxamide类似物G_2具有良好的活性,尤其对人乳腺癌细胞株(MCF-7)具有较好的细胞毒性,其IC_(50)值为5.85 mg/L。Using N-[（ 9H-Fluoren-9-ylmethoxy） carbonyl]-leucine（ Fmoc-Leu-OH） and N-[（ 9HFluoren-9-ylmethoxy） carbonyl]-proline（ Fmoc-Pro-OH） as starting materials,the classic Fmoc solid phase synthesis scheme for cyclopentapetide was employed. The linear peptapeptides were synthesized by protecting and deprotecting the amine of amino acid,the amino acid methylation,condensation and other steps. The cyclization step was completed by benzotriazol-1-yl-oxytripyrrolidinophosphonium hexafluorophosphate（ Py BOP） as a coupling reagent. Two Galaxamide analogues G1 and G2 were obtained and they had a yield of cyclization of 59. 5% and 41. 1%,respectively. Their structures were characterized by means of ^1HNMR,^13CNMR and ESI-MS. The anti- tumor activities in vitro of G1 and G2were investigated through the MTT assay against human cancer cell lines The results demonstrated that proline-containing Galaxamide analogue G2 possessed potent cytotoxicity on human breast cancer cell line（ MCF-7） with an IC50 value of 5. 85 mg / L.

关 键 词：Fmoc固相合成 环五肽 Galaxamide 六氟磷酸苯并三唑-1-基氧基三吡咯烷基磷 抗肿瘤活性 医药原料 

分 类 号：O629.72[理学—有机化学]