摘要
通过在细胞生长抑制剂Dolastatin15(D15)的N端引入含环胺基的非天然氨基酸1～3,赋予其构象限制和疏水性,设计合成了21个结构类似物,并进行了体外抑制肿瘤细胞生长的活性评价.结果表明,部分化合物显示出较好的抑制肿瘤细胞生长活性,同时探讨了初步的构效关系.
Dolastatin 15 （D15）was a linear depsipeptide with two N-methylated valines and a complex C-terminal, showing potent cell growth inhibitory activity. D15 was highly alkylation and with spacial constraints. Modifications at D15＇s N-terminal were performed by introducing three unnatural amino acid analogs 1--3 with more conformation-restriction and hydrophobicity. Twenty-one compounds were synthesized, and their activities were evaluated in vitro on human tumor cell lines K562, OVCA2780 and Kato-Ⅲ. Some compounds exhibited modest potency compared to compound LU103793, an analog of D15, evaluated in clinical phase Ⅱ now. A primary structure-activity relationship was summarized about the N-terminal.
出处
《高等学校化学学报》
SCIE
EI
CAS
CSCD
北大核心
2009年第2期308-313,共6页
Chemical Journal of Chinese Universities
