Design, synthesis and antiproliferative activity of novel substituted 2-amino-7,8-dihydropteridin-6(5H)-one derivatives

被引：6

作者：

Li, Qiu ^{[1
]}

Yang, Hai-Kui ^{[1
]}

Sun, Qi ^{[1
]}

You, Wen-Wei ^{[1
]}

Zhao, Pei-Liang ^{[1
]}

机构：

[1] Southern Med Univ, Sch Pharmaceut Sci, Guangdong Prov Key Lab New Drug Screening, Guangzhou 510515, Guangdong, Peoples R China

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2017年 / 27卷 / 17期

基金：

中国国家自然科学基金;

关键词：

Dihydropteridinones; Synthesis; Antiproliferative activity; ONE-POT SYNTHESIS; PROTOPORPHYRINOGEN OXIDASE-INHIBITORS; BEARING 1,2,4-TRIAZOLE MOIETY; BIOLOGICAL EVALUATION; OPTIMIZATION;

D O I：

10.1016/j.bmcl.2017.07.076

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Based on our previous work, a series of novel 2-amino-7,8-dihydropteridin-6(5H)-one derivatives were designed and synthesized via a ring-closing strategy. Biological evaluation with four human cancer cell lines (BT549, T47D, MDA-MB-468, and MDA-MB-231) showed that most of these compounds possessed moderate to potent antiproliferative activities. The most promising compound 8-benzyl-2-(phenethy-lamino)-7,8-dihydropteridin-6(5H)-one (6q) possessing IC50 values of 7.75, 6.37, and 10.73 mu M against MDA-MB-468, T47D, and BT549, respectively, which were 49, 11, and 8 folds more active than the positive control fluorouracil. Moreover, fluorescence-activated cell sorting analysis revealed that compound 6q displayed a significant effect on G1 cell-cycle arrest in a concentration-dependent manner in T47D cells. The initial structure-activity relationship studies indicated that linker-length of amine chain in C-2 position of pyrimidine ring played a crucial role in modulating the antitumor activity, which could be of help in the rational design of dihydropteridin-6(5H)-ones as novel anticancer drugs. (C) 2017 Elsevier Ltd. All rights reserved.

引用

页码：3954 / 3958

页数：5

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