预测两种从东北马兜铃中新分离出的含菲醚环化合物作为细胞周期蛋白依赖性激酶2（CDK2）抑制剂的可能性。

Predicting the possibility of two newly isolated phenetheren ring containing compounds from Aristolochia manshuriensis as CDK2 inhibitors.

作者信息

Alshatwi Ali Abdullah, Hasan Tarique Noorul, Syed Naveed Ahmed, Shafi Gowhar

机构信息

Molecular Cancer Biology Research Lab, Dept. of Food Science and Nutrition, College of Food and Agricultural Sciences, King Saud University, Saudi Arabia.

出版信息

Bioinformation. 2011;7(7):334-8. doi: 10.6026/97320630007334. Epub 2011 Dec 10.

UNLABELLED

Aristolochia manshuriensis has been used for centuries in Chinese medicinal system for their versatile medicinal uses. Recent studies have revealed two new aristolactames (compound A and B) with γ-lactame ring fused with the phenentherene ring as potent inhibitors of human Cycline Dependent Kinase2 (CDK2). Studies on aristolactames and related compounds claim for their CDK2 inhibition without delineating the involved mechanism and structural basis of interaction. Molecular structural model was used to we propose a structural basis of CDK2 inhibition. We showed that these compounds (A and B) can successfully dock into the inhibitor binding pockets of human CDK2. Predicted binding affinities are comparable to known inhibitors of CDK2. Results were in agreement with the earlier biochemical studies. Hence, suggest that studied compounds A and B can be a promising scaffold for rational design of novel and potential drugs against cancer.

ABBREVIATIONS

CDK2 - cyclin-dependent kinase 2, OLO - Olomoucine, NW1 - Cyclohexylmethyloxy-5-Nitroso-Pyrimidine- 2, 4-Diamine, CMG - 6-O-Cyclohexylmethyl Guanine.

未标注

东北马兜铃在中国医药体系中已有数百年的使用历史，因其具有多种药用价值。最近的研究发现了两种新的马兜铃内酰胺（化合物A和B），它们的γ-内酰胺环与菲环稠合，是人类细胞周期蛋白依赖性激酶2（CDK2）的有效抑制剂。关于马兜铃内酰胺及相关化合物的研究表明它们具有CDK2抑制作用，但未阐明其作用机制和相互作用的结构基础。我们利用分子结构模型提出了CDK2抑制的结构基础。我们发现这些化合物（A和B）能够成功对接至人类CDK2的抑制剂结合口袋。预测的结合亲和力与已知的CDK2抑制剂相当。结果与早期的生化研究一致。因此，表明所研究的化合物A和B可能是合理设计新型抗癌潜在药物的有前景的支架。