Puttaraju Kallimeledoddi B, Mahesh Sankanahally Srinivasshetty, Shivashankar Kalegowda, Lokanath Neratur Krishnappagowda, Madegowda Mahendra
Department of Studies in Physics, Manasagangotri, University of Mysore, Mysore- 570006, India.
P. G. Department of Chemistry, Central College Campus, Bangalore University, Bangalore- 560001, India.
Bioinformation. 2014 May 20;10(5):288-92. doi: 10.6026/97320630010288. eCollection 2014.
Protein kinases are important drug targets in human cancers, inflammation and metabolic diseases. Docking studies was performed for all the benzimidazopyrimidine and coumarin substituted benzimidazopyridimine derivatives with human Aurora A kinase target (3FDN) employing flexible ligand docking approach by using AutoDock 4.2. All the compounds were found to have minimum binding energy ranging from -6.26 to -9.29 kJ/mol. Among the molecules tested for docking study, 10-(6-Bromo-2-oxo- 2H-chromen-4-ylmethyl)-2-isopropyl-10H-benzo[4,5]imidazo[1,2-a]pyrimidin-4-one (2k) showed minimum binding energy (-9.29 kJ/mol) with ligand efficiency of -0.31. All the ligands were docked deeply within the binding pocket region of 3FDN showing hydrogen bonds with Ala 213 and Asn 261. The docking study results showed that these derivatives are excellent inhibitor of human Aurora A kinase target; and also all these docked compounds have good inhibition constant, vdW + Hbond + desolv energy with best RMSD value.
蛋白激酶是人类癌症、炎症和代谢疾病中的重要药物靶点。采用AutoDock 4.2的柔性配体对接方法，对所有苯并咪唑并嘧啶和香豆素取代的苯并咪唑并嘧啶衍生物与人极光激酶A靶点（3FDN）进行了对接研究。发现所有化合物的最小结合能在-6.26至-9.29 kJ/mol之间。在对接研究测试的分子中，10-(6-溴-2-氧代-2H-色烯-4-基甲基)-2-异丙基-10H-苯并[4,5]咪唑并[1,2-a]嘧啶-4-酮（2k）显示出最小结合能（-9.29 kJ/mol），配体效率为-0.31。所有配体都深深地对接在3FDN的结合口袋区域内，与丙氨酸213和天冬酰胺261形成氢键。对接研究结果表明，这些衍生物是人类极光激酶A靶点的优秀抑制剂；而且所有这些对接化合物都具有良好的抑制常数、范德华力+氢键+去溶剂化能以及最佳的均方根偏差值。
