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NISCAIR ONLINE PERIODICALS REPOSITORY (NOPR) >
NISCAIR PUBLICATIONS >
Research Journals >
Indian Journal of Chemistry -Section B (IJC-B) >
IJC-B Vol.51B [2012] >
IJC-B Vol.51B(12) December 2012] >
| Title: | QSAR analysis on inhibitors of human dihydroorotate dehydrogenase
(hDHODH): The aryl carboxylic acid amide derivatives |
| Authors: | Vyas, Vivek K
Ghate, Manjunath |
| Keywords: | QSAR
Dihydroorotate dehydrogenase (DHODH)
Aryl carboxylic acid amides
hDHODH inhibitors
LogP
LUMO |
| Issue Date: | Dec-2012 |
| Publisher: | NISCAIR-CSIR, India |
| Abstract: | Structural and
physicochemical requirements of aryl carboxylic acid amide derivatives for the
inhibition of human dihydroorotate dehydrogenase (hDHODH) are explored in this QSAR study.
The calculated molecular descriptors (electronic and thermodynamic) have been
used to derive QSAR models between hDHODH
inhibitory activity and structural properties. The best model for prediction of
hDHODH inhibitory activity is obtained
by applying sequential multiple linear regression (SMLR) analysis. Regression
coefficient of all the descriptors is significant at more than 99% and statistically
significant model with r2 > 0.87 is obtained. Selected QSAR model
emphasized the importance of logP, torsion
energy (Et), 1,4-dihedral van
der Waals interaction (1,4-VDWE) and electronic descriptor like lowest unoccupied molecular
orbital (LUMO) on hDHODH inhibitory
activity. Results of QSAR analysis show that logP and LUMO are the principle
descriptors for inhibition of hDHODH.
QSAR model has also been tested successfully for internal (q2 >
0.753) and external (r2 pred > 0.621)
validation criteria. It is believed that the results of this study will
be helpful in the design of more potent and selective hDHODH inhibitors.
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| Page(s): | 1749-1760 |
| CC License: |  CC Attribution-Noncommercial-No Derivative Works 2.5 India |
| ISSN: | 0975-0983(Online); 0376-4699(Print) |
| Source: | IJC-B Vol.51B(12) December 2012]
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