3D-QSAR studies of heterocyclic quinones with inhibitory activity on vascular smooth muscle cell proliferation using pharmacophore-based alignment

Chung Kyu Ryu, Yoonji Lee, Seul gi Park, Hea Jung You, Ra Young Lee, Seung Yon Lee, Sun Choi

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

The abnormal proliferation and migration of vascular smooth muscle cells (SMCs) play an important role in the pathology of coronary artery atherosclerosis and restenosis following angioplasty. It was reported that some heterocyclic quinone derivatives such as 6-arylamino-quinoxaline-5,8-diones and 6-arylamino-1H-benzo[d]imidazole-4,7-diones have inhibitory activity on rat aortic smooth muscle cell (RAoSMC) proliferation. To understand the structural basis for antiproliferative activity to design more potent agents, we generated pharmacophore models of representative molecules with high activity using Genetic Algorithm with Linear Assignment of Hypermolecular Alignment of Database (GALAHAD) and aligned a series of compounds to the selected pharmacophore model, then performed three-dimensional quantitative structure-activity relationship (3D-QSAR) studies using Comparative Molecular Field Analysis (CoMFA) and Comparative Molecular Similarity Indices Analysis (CoMSIA). Good cross-validated correlations were obtained with CoMFA (resulting in q2 of 0.734 and r2 of 0.947) and CoMSIA (resulting in q2 of 0.736 and r2 of 0.913). The IC50 values of the heterocyclic quinone derivatives on RAoSMC exhibited a strong correlation with steric and hydrophobic fields of the 3D structure of the molecules, resulting in the reliable prediction of inhibitory activity of the series of compounds.

Original languageEnglish
Pages (from-to)9772-9779
Number of pages8
JournalBioorganic and Medicinal Chemistry
Volume16
Issue number22
DOIs
StatePublished - 15 Nov 2008

Keywords

  • 1H-benzo[d]imidazole-4,7-dione
  • Antiproliferative
  • CoMFA
  • CoMSIA
  • QSAR
  • Quinoxaline-5,8-dione
  • Vascular smooth muscle cell

Fingerprint

Dive into the research topics of '3D-QSAR studies of heterocyclic quinones with inhibitory activity on vascular smooth muscle cell proliferation using pharmacophore-based alignment'. Together they form a unique fingerprint.

Cite this