Title of article :
Comparative molecular field analysis and comparative molecular similarity indices analysis of boron-containing human thymidine kinase 1 substrates Original Research Article
Author/Authors :
Achintya K. Bandyopadhyaya، نويسنده , , Rohit Tiwari، نويسنده , , Werner Tjarks، نويسنده ,
Issue Information :
روزنامه با شماره پیاپی سال 2006
Pages :
9
From page :
6924
To page :
6932
Abstract :
Three-dimensional quantitative structure–activity relationship (3D-QSAR) using CoMFA and CoMSIA techniques was applied to evaluate 56 pyrimidine nucleosides as substrates of human thymidine kinase 1 (hTK1), 27 of them containing a carborane substituent either at the 3-, 5-, or 3′-position of the 2′-deoxyuridine scaffold. This is the first report describing 3D-QSAR studies of compounds containing boron atoms. Both CoMFA and CoMSIA models were derived from a training set of 47 molecules and the predictive capacity of the CoMSIA model was successfully validated by accurately calculating known phosphorylation rates of both boronated and non-boron hTK1 substrates that were not included in the training set. The optimal CoMSIA model provided the following values: q2 0.622, r2 0.983, s 0.165, and F 187.5. Contour maps obtained from the CoMSIA model were in agreement with the experimentally determined biological data.
Keywords :
Human thymidine kinase 1 (hTK1) , phosphorylation , Boron neutron capture therapy (BNCT) , 3D-QSAR , CoMFA , CoMSIA , 3-Carboranyl thymidine analogues (3CTAs)
Journal title :
Bioorganic and Medicinal Chemistry
Serial Year :
2006
Journal title :
Bioorganic and Medicinal Chemistry
Record number :
1305183
Link To Document :
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