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KMID : 0043320090320030317
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Archives of Pharmacal Research
2009 Volume.32 No. 3 p.317 ~ p.323
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Pharmacophore-based 3D-QSAR of HIF-1 Inhibitors
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Lee Kyeong
Lee Jung-Joon
Won Mi-Sun
Cho Seung-Joo
Pasha F.A.
Chung Jae-Yoon
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Abstract
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(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 dimensionalquantitative 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.
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KEYWORD
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CoMFA, CoMSIA, Drug design, Pharmacophore, HIF-1 Inhibitor, 3D-QSAR
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