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Structural studies of B-type Aurora kinase inhibitors using computational methods.

ABSTRACT: AIM: To characterize the structural features of quinazoline-based Aurora B inhibitors that influence its inhibitor activity. METHODS: Two geometrical methods, Method 1 and Method 2, were used to develop the 3D-QSAR models. The most active ligand was used as the template for the alignment of all the ligands in Method 1, and a conformer of the cocrystal ligand was used as the template for the alignment of all the ligands in Method 2. RESULTS: The models suggest that highly active ligands can be designed by varying the R1 substituent at position 7 of the quinazoline ring with positively charged, bulky, hydrophobic groups, while bulky and hydrophobic groups around the thiazole ring are desirable for higher activity. CONCLUSION: This study emphasizes that the bioactive conformer is rather different from the minima. The steric, electrostatic, and hydrophobic field effects contribute to its inhibitory activity.

SUBMITTER: Neaz M

PROVIDER: S-EPMC4002836 | biostudies-literature | 2010 Feb

REPOSITORIES: biostudies-literature

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Structural studies of B-type Aurora kinase inhibitors using computational methods.

Neaz Mm M Muddassar M M Pasha Fa F Cho Seung Joo SJ

Acta pharmacologica Sinica 20100201 2

<h4>Aim</h4>To characterize the structural features of quinazoline-based Aurora B inhibitors that influence its inhibitor activity.<h4>Methods</h4>Two geometrical methods, Method 1 and Method 2, were used to develop the 3D-QSAR models. The most active ligand was used as the template for the alignment of all the ligands in Method 1, and a conformer of the cocrystal ligand was used as the template for the alignment of all the ligands in Method 2.<h4>Results</h4>The models suggest that highly activ ...[more]

PMID: 20139908

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