Synthesis and antitumor activity of thieno-separated tricyclic purines
Synthesis and antitumor activity of thieno-separated tricyclic purines
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DOI：
10.1021/jm000326i
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发表时间：
2000-12-14
影响因子：
7.3
通讯作者：
Dransfield, DT
中科院分区：
文献类型：
--
作者：
Seley, KL;Januszczyk, P;Dransfield, DT
嘌呤环系统无疑是自然界中最普遍的杂环系统之一，因为它具有作为无数生物相关衍生物中的母环的区别。因此，修饰嘌呤具有影响多个领域的潜力也就不足为奇了，包括更好地了解 DNA 损伤剂的生物效应、酶/底物相互作用以及开发更有效的药物。我们佐治亚理工学院研究的一个重点是设计和合成一系列含有杂环间隔环的扩展嘌呤类似物，并对其用途进行研究（i）潜在的抗癌和抗病毒药物，i（ii）酶和辅酶结合位点的三维探针，以及（iii）DNA小沟的结构探针。本文描述了两种噻吩并分离的嘌呤类似物的合成和初步抗肿瘤活性；以三溴咪唑为原料，经过12步合成三环1，总收率为7%；三环2的合成经过9步，总收率为13%。 1和2：在体外对HCT116结直肠癌细胞表现出生长抑制作用。
The purine ring system is undoubtedly one of the most ubiquitous heterocyclic ring systems in nature as it has the distinction of being the parent ring in countless derivatives of biological relevance. It is not surprising then that modified purines possess the potential to impact several areas, including a better understanding of the biological effects of DNA damaging agents, enzyme/substrate interactions, and in the development of more potent medicinal agents. One focus for our research at Georgia Tech has centered around the design and synthesis of a series of extended purine analogues containing a heterocyclic spacer ring, with sites set on investigations into their use gs (i) potential anticancer and antiviral agents,i(ii) dimensional probes for enzyme and coenzyme binding sites, and (iii) structural probes of the minor groove of DNA. The synthesis and preliminary;antitumor activity of two thieno-separated purine analogues are described herein; Tricyclic 1 was synthesized in 12 steps from tribromoimidazole and with an overall yield of 7%; Tricyclic 2 was synthesized in 9 steps with an overall yield of 13%. Both 1 and 2:exhibited growth inhibitory effects on HCT116 colorectal cancer cells in vitro.