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

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.

Figure 1

Structure of (A) Bennzimidazopyrimidine (B) Coumarin substituted benzimidazopyridimine derivatives.

Figure 2

Ligplot results of Aurora A (3FDN), showing the binding of ligand Mmh 1(A) with amino acid residues present in an active site pocket.

Figure 3

Enfolding of molecules 2e, 2f, 2h and 2k in the active site pocket

Figure 4

H-bond interaction of ligand molecules (2e, 2f, 2h and 2k) with 3FDN