Molecular docking studies of benzimidazopyrimidine and coumarin substituted benzimidazopyrimidine derivatives: As potential human Aurora A kinase inhibitors

Chandra; Kallimeledoddi B Puttaraju; Sankanahally Srinivasshetty Mahesh; Kalegowda Shivashankar; Neratur Krishnappagowda Lokanath; Mahendra Madegowda

doi:10.6026/97320630010288

Molecular docking studies of benzimidazopyrimidine and coumarin substituted benzimidazopyrimidine derivatives: As potential human Aurora A kinase inhibitors

Bioinformation. 2014 May 20;10(5):288-92. doi: 10.6026/97320630010288. eCollection 2014.

Authors

Chandra¹, Kallimeledoddi B Puttaraju², Sankanahally Srinivasshetty Mahesh³, Kalegowda Shivashankar², Neratur Krishnappagowda Lokanath¹, Mahendra Madegowda¹

Affiliations

¹ Department of Studies in Physics, Manasagangotri, University of Mysore, Mysore- 570006, India.
² P. G. Department of Chemistry, Central College Campus, Bangalore University, Bangalore- 560001, India.
³ Department of Physics, Acharya Institute of Technology, Bangalore- 560090, India.

Abstract

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.

Keywords: Aurora A; Benzimidazopyrimidine and coumarin substituted benzimidazopyridimine derivatives; Docking studies; Single crystal structure.