Abstract
(Aryloxyamino)benzoic acids and nicotinic/isonicotinic acids represent an important new class of small molecules that inhibit the activation of Hypoxia-Inducible Factor (HIF)-1. In order to understand the factors affecting inhibitory potency of HIF-1 inhibitors, 3 dimensional-quantitative structure activity relationship (3D-QSAR) studies were performed. Since no receptor structure are available, the pharmacophore-based alignment was used for comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA). The CoMFA and CoMSIA models gave reasonable statistics (CoMFA: q2 = 0.564, r2=0.945; CoMSIA: q2 = 0.575, r2=0.929). Both CoMFA and CoMSIA results indicate that the steric interaction is a major factor, while CoMSIA suggests importance of hydrogen bonding. These findings about steric and H-bonding effects can be useful to design new inhibitors.
Original language | English |
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Pages (from-to) | 317-323 |
Number of pages | 7 |
Journal | Archives of Pharmacal Research |
Volume | 32 |
Issue number | 3 |
DOIs | |
State | Published - Mar 2009 |
Keywords
- 3D-QSAR
- CoMFA
- CoMSIA
- Drug design
- HIF-1 Inhibitor
- Pharmacophore