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Internet Electronic Journal of Molecular Design - IEJMD, ISSN 1538-6414, CODEN IEJMAT
| ABSTRACT - Internet Electron. J. Mol. Des. March 2009, Volume 8, Number 3, 29-41 |
Analog Based Studies on Cathepsin B Inhibitors to Design Novel Lead
Compounds for the Treatment of Cancer
L. Jayashankar, B. Syama Sundar, Shruti Awasthi, and B. Madhulika
Internet Electron. J. Mol. Des. 2009, 8, 29-41
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Abstract:
We have performed analog based design along with pharmacophore hypothesis
development on a series of cathepsin B inhibitors. We intend to utilize
the pharmacophore information to undertake 3D searches on large databases to
identify novel lead candidate against cathepsin B inhibitors for the treatment of cancer.
Molecular field analysis (MFA) and receptor surface analysis (RSA) methods
have been carried out to derive best QSAR models. Catalyst version 4.7 was
used to generate pharmacophore models. The QSAR models developed by MFA
and RSA methods have r2 values of 0.77 and 0.879,
respectively. The best quantitative pharmacophore model showed
two hydrogen bond acceptor, one hydrophobic aliphatic and one
ring aromatic feature. The 3D QSAR study shows that hydrophobic groups are
responsible for an increase in activity, and indicate that RSA predicts
better than MFA. Further, the knowledge of the four-feature pharmacophore
hypothesis for cathepsin B inhibitors can be very useful for virtual
screening to design more potent lead compounds.
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