Pharmacophore-based 3D-QSAR of HIF-1 inhibitors

Jae Yoon Chung, F. A. Pasha, Seung Joo Cho, Misun Won, Jung Joon Lee, Kyeong Lee

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

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 languageEnglish
Pages (from-to)317-323
Number of pages7
JournalArchives of Pharmacal Research
Volume32
Issue number3
DOIs
StatePublished - Mar 2009

Keywords

  • 3D-QSAR
  • CoMFA
  • CoMSIA
  • Drug design
  • HIF-1 Inhibitor
  • Pharmacophore

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