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-(phenethylamino)-7,8-dihydropteridin-6(5H)-one (6q) possessing IC₅₀ values of 7.75, 6.37, and 10.73 μM 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.

基于我们以前的工作，设计了一系列新颖的2-氨基-7,8-二氢蝶呤-6（5 H）-one衍生物，并通过闭环策略进行了合成。用四种人类癌细胞系（BT549，T47D，MDA-MB-468和MDA-MB-231）进行生物学评估，结果表明，这些化合物大多数都具有中度到强效的抗增殖活性。最有前途的化合物8-苄基-2-（苯乙氨基）-7,8-二氢蝶呤-6（5 H）-一（6q）对MDA-MB-468，T47D的IC ₅₀值为7.75、6.37和10.73μM和BT549的活性分别比阳性对照氟尿嘧啶高49倍，11倍和8倍。此外，荧光激活细胞分选分析表明化合物6q在T47D细胞中以浓度依赖的方式显示了对G1细胞周期停滞的显着影响。初步的结构与活性关系研究表明，嘧啶环C-2位的胺链接头长度在调节抗肿瘤活性中起关键作用，这可能有助于二氢蝶呤-6（5 H）的合理设计。-一种新的抗癌药。