Structural requirements for imidazo[1,2-a]pyrazine derivatives as Aurora A kinase inhibitors and validation of the model

Aurora kinases belong to the family of serine/threonine kinases. They are divided into three subclasses, Aurora A kinase, Aurora B kinase, and Aurora C kinase and are reported to be vital for cell proliferation. Abnormal expression of these enzymes leads to cancer. Predictive CoMFA and CoMSIA based...

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Bibliographic Details
Published in:Medicinal chemistry research 2014-12, Vol.23 (12), p.5215-5223
Main Authors: Kanhed, Ashish M., Zambre, Vishal P., Pawar, Vijay A., Sharma, Mayank Kumar, Giridhar, Rajani, Yadav, Mange Ram
Format: Article
Language:English
Subjects:
Biochemistry
Biomedical and Life Sciences
Biomedicine
Cell Biology
Original Research
Pharmacology/Toxicology
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Summary:Aurora kinases belong to the family of serine/threonine kinases. They are divided into three subclasses, Aurora A kinase, Aurora B kinase, and Aurora C kinase and are reported to be vital for cell proliferation. Abnormal expression of these enzymes leads to cancer. Predictive CoMFA and CoMSIA based quantitative structure activity relationship models have been developed on 51 imidazo[1,2- a ]pyrazine derivatives reported previously by Merck Research Laboratories. AutoDock was used for docking of the most active compound ( 34 ) and the conformation thus obtained was used for the alignment of 3D structures. The developed (CoMSIA-SEHD) model showed good predictive ability with predictive squared correlation coefficient ( r 2 ) value of 0.752. The best model was validated systematically using different validation parameters. The CoMSIA model gave useful information to understand features required to modify and develop new potential Aurora kinase inhibitors.
ISSN:1054-2523
1554-8120
DOI:10.1007/s00044-014-1094-x