Design, synthesis, and SAR of embelin analogues as the inhibitors of PAI-1 (plasminogen activator inhibitor-1)

Fanglei Chen; Guiping Zhang; Zebin Hong; Zhonghui Lin; Min Lei; Mingdong Huang; Lihong Hu

doi:10.1016/j.bmcl.2014.03.045

Design, synthesis, and SAR of embelin analogues as the inhibitors of PAI-1 (plasminogen activator inhibitor-1)

Bioorg Med Chem Lett. 2014 May 15;24(10):2379-82. doi: 10.1016/j.bmcl.2014.03.045. Epub 2014 Mar 24.

Authors

Fanglei Chen¹, Guiping Zhang¹, Zebin Hong², Zhonghui Lin², Min Lei¹, Mingdong Huang³, Lihong Hu⁴

Affiliations

¹ Shanghai Research Center for the Modernization of Traditional Chinese Medicine, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, PR China.
² State Key Laboratory of Structural Chemistry, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou 350002, PR China.
³ State Key Laboratory of Structural Chemistry, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou 350002, PR China. Electronic address: mhuang@fjirsm.ac.cn.
⁴ Shanghai Research Center for the Modernization of Traditional Chinese Medicine, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, PR China. Electronic address: lhhu@simm.ac.cn.

PMID: 24731276
DOI: 10.1016/j.bmcl.2014.03.045

Abstract

The natural product embelin was found to have PAI-1 inhibitory activity with the IC50 value of 4.94μM. Based on the structure of embelin, a series of analogues were designed, synthesized, and evaluated for their ability to inhibit PAI-1. The SAR study on these compounds disclosed that the inhibitory potency largely depended on the hydroxyl groups at C2 and C5, and the length of the alkyl chains at C3 and C6. Compound 11 displayed the best PAI-1 inhibitory potency with the IC50 value of 0.18μM.

Keywords: Embelin; Inhibitory activity; Natural product; PAI-1; SAR study.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Benzoquinones / chemical synthesis
Benzoquinones / chemistry*
Benzoquinones / pharmacology*
Binding Sites
Drug Design
Models, Molecular
Plasminogen Activator Inhibitor 1 / chemistry*
Plasminogen Activator Inhibitor 1 / metabolism*
Structure-Activity Relationship

Substances

Benzoquinones
Plasminogen Activator Inhibitor 1
embelin