1. Pharmacophore-based 3D-QSAR of HIF-1 inhibitors.
- Author
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Chung JY, Pasha FA, Cho SJ, Won M, Lee JJ, and Lee K
- Subjects
- Antineoplastic Agents pharmacology, Benzoates chemistry, Hydrogen Bonding, Hypoxia-Inducible Factor 1 antagonists & inhibitors, Isonicotinic Acids chemistry, Least-Squares Analysis, Ligands, Molecular Structure, Nicotinic Acids chemistry, Protein Conformation, Reproducibility of Results, Antineoplastic Agents chemistry, Computer-Aided Design, Drug Design, Hypoxia-Inducible Factor 1 chemistry, Imaging, Three-Dimensional, Models, Molecular, Quantitative Structure-Activity Relationship
- 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: q(2) = 0.564, r(2)=0.945; CoMSIA: q(2) = 0.575, r(2)=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.
- Published
- 2009
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