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Indian Journal of Biochemistry and Biophysics (IJBB) >
IJBB Vol.47 [2010] >
IJBB Vol.47(4) [August 2010] >
| Title: | Homology modeling and QSAR analysis of 1,3,4-thiadiazole and 1,3,4-triazole derivatives as carbonic anhydrase inhibitors |
| Authors: | Akula, N V Murali Krishna
Kumar, Surendra
Singh, Vineet
Tiwari, Meena |
| Keywords: | Carbonic anhydrase inhibitor
QSAR
Anti-tumor
Homology
Modeller 9v2 |
| Issue Date: | Aug-2010 |
| Publisher: | CSIR |
| Abstract: | Carbonic
anhydrase (CA) inhibitors are very interesting target for designing anticancer
(hypoxic) and antiglaucoma drugs. In the present study, a 3D homology modeling
of human carbonic anhydrase-IX (hCA-IX) isozyme, based upon the crystal
structure of murine CA-XIVA (PDB CODE 1RJ5) was performed, as no experimental
3D structures are available.
A homology model of hCA-IX was developed and validated. To explore the
responsible physicochemical properties of 1,3,4-thiadiazole and 1,3,4-triazole
derivatives for carbonic anhydrase inhibition, a quantitative structure activity
relationship (QSAR) study was performed having hCA-II and hCA-IX inhibitory
activity respectively. In hCA-II and
hCA-IX inhibitory activities, four significant models with good correlations ( 0.945 & 0.926) were obtained; two models (models
1 and 3) were selected based on statistical criterion. The QSAR study revealed
that in case of hCA-II, overall increase in size and volume of molecule,
introduction of electropositive surfaces might increase the inhibitory
activity, whereas in case of hCA-IX, decreasing the hydrophobicity and
introduction of electron releasing substituents might increase the hCA-IX inhibitory
activity. |
| Page(s): | 234-242 |
| ISSN: | 0975-0959 (Online); 0301-1208 (Print) |
| Source: | IJBB Vol.47(4) [August 2010]
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