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作为激酶抑制剂的嘌呤类似物:综述

Purine Analogues as Kinase Inhibitors: A Review.

作者信息

Sharma Sahil, Mehndiratta Samir, Kumar Sunil, Singh Jagjeet, Bedi Preet M S, Nepali Kunal

机构信息

Department of Pharmaceutical Chemistry, ISF College of Pharmacy, Moga, Punjab -142001, India.

出版信息

Recent Pat Anticancer Drug Discov. 2015;10(3):308-41. doi: 10.2174/1574892810666150617112230.

Abstract

Protein kinases constitute one of the largest and most functionally diverse gene families that regulate key cell functions. In past several years, kinase inhibition has emerged as potential anti-cancer drug target. Purine is a priveleged heterocyclic nucleus which exists in the chemical architecture of various bioactive compounds. Numerous reports on the use of purine analogues in the treatment of acute leukemias (thiopurines, pentostatin), as antiviral (acyclovir, penciclovir, ganciclovir), as immunosuppressive (azathioprine), as antitumor (vidarabine), as bronchodilator (theophylline) have been revealed. In the past decade, purine analogues have emerged as significantly potent kinase inhibitors. A fair amount of research has been done and several patents have also been published highlighting the kinase inhibitory action of purines. Caffeine, 2-aminopurine, purvalanol-A, seleciclib, FSBA, adenosine thiol analogue possessing purine as the basic moiety fall under this category. In view of the use of purines for the inhibition of kinases, there is need for compilation of data specifying the prominence of purines in the treatment of cancer through this mechanism. The structure of the potent compounds, their IC50 values, models used and the enzymes/ receptors/ targets involved have been presented in this review. The present compilation covers the patents published entailing the purines as kinase inhibitors and the purine drugs employed in chemotherapy.

摘要

蛋白激酶构成了调节关键细胞功能的最大且功能最多样化的基因家族之一。在过去几年中,激酶抑制已成为潜在的抗癌药物靶点。嘌呤是一种特权杂环核,存在于各种生物活性化合物的化学结构中。关于嘌呤类似物在治疗急性白血病(硫嘌呤、喷司他丁)、作为抗病毒药物(阿昔洛韦、喷昔洛韦、更昔洛韦)、作为免疫抑制剂(硫唑嘌呤)、作为抗肿瘤药物(阿糖腺苷)、作为支气管扩张剂(茶碱)方面的众多报道已被揭示。在过去十年中,嘌呤类似物已成为显著有效的激酶抑制剂。已经进行了大量研究,并且也发表了几项专利,突出了嘌呤的激酶抑制作用。咖啡因、2-氨基嘌呤、嘌呤醇-A、司立西利、FSBA、以嘌呤为基本部分的腺苷硫醇类似物都属于这一类。鉴于嘌呤用于抑制激酶,需要汇编数据以明确嘌呤通过这种机制在癌症治疗中的突出地位。本综述介绍了有效化合物的结构、它们的IC50值、所使用的模型以及涉及的酶/受体/靶点。本汇编涵盖了已发表的将嘌呤作为激酶抑制剂以及用于化疗的嘌呤药物的专利。

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