Department of S & H (Computer Applications), Sathyabama University, Chennai, India.
J Mol Model. 2013 Sep;19(9):3581-9. doi: 10.1007/s00894-013-1887-8. Epub 2013 Jun 1.
On the basis of stereo specific information obtained from crystal structures of CDK2, indole and chromene analogues were designed by suitably substituting the pharmacophores on their moiety and docked with target protein for calculating binding affinities. The binding affinities are represented in glide score. (5E)-5-[(1-methyl-1H-indol-3-yl)methylidene]-2,4,6-trioxotetrahydro-2H-pyrimidin-1-ide (I1), (5E)-5-(1H-indol-3-ylmethylidene)-2,4,6-trioxotetrahydro-2H-pyrimidin-1-ide (I2) and 2-amino-4-(4-methyl phenyl)-5-oxo-5,6,7,8-tetrahydro-4H-chromene-3-carbonitrile (C9) were selected for synthesis and biological testing based on vital interactions. (5E)-5-(1H-indol-3-ylmethylidene)-2,4,6-trioxotetrahydro-2H-pyrimidin-1-ide(I2) and 2-amino-4-(4-methyl phenyl)-5-oxo-5,6,7,8-tetrahydro-4H-chromene-3-carbonitrile (C9) were proved to be active against MCF-7 and HeLa cell lines.
基于从 CDK2 的晶体结构中获得的立体特异性信息，通过适当取代其部分的药效团，设计了吲哚和色烯类似物，并与靶蛋白对接以计算结合亲和力。结合亲和力用 Glide 得分表示。(5E)-5-[(1-甲基-1H-吲哚-3-基)亚甲基]-2,4,6-三氧代四氢-2H-嘧啶-1-基)（I1）、(5E)-5-(1H-吲哚-3-基亚甲基)-2,4,6-三氧代四氢-2H-嘧啶-1-基)（I2）和 2-氨基-4-(4-甲基苯基)-5-氧代-5,6,7,8-四氢-4H-色烯-3-甲腈（C9）被选择用于合成和基于重要相互作用的生物测试。(5E)-5-(1H-吲哚-3-基亚甲基)-2,4,6-三氧代四氢-2H-嘧啶-1-基（I2）和 2-氨基-4-(4-甲基苯基)-5-氧代-5,6,7,8-四氢-4H-色烯-3-甲腈（C9）被证明对 MCF-7 和 HeLa 细胞系具有活性。
