Mono-carbonyl curcumin analogues as 11β-hydroxysteroid dehydrogenase 1 inhibitors

Han Lin; Guo-Xin Hu; Jingjing Guo; Yufei Ge; Guang Liang; Qing-Quan Lian; Yanhui Chu; Xiaohuan Yuan; Ping Huang; Ren-Shan Ge

doi:10.1016/j.bmcl.2013.05.080

Mono-carbonyl curcumin analogues as 11β-hydroxysteroid dehydrogenase 1 inhibitors

Bioorg Med Chem Lett. 2013 Aug 1;23(15):4362-6. doi: 10.1016/j.bmcl.2013.05.080. Epub 2013 Jun 11.

Authors

Han Lin¹, Guo-Xin Hu, Jingjing Guo, Yufei Ge, Guang Liang, Qing-Quan Lian, Yanhui Chu, Xiaohuan Yuan, Ping Huang, Ren-Shan Ge

Affiliation

¹ The 2nd Affiliated Hospital & Institute of Reproductive Biomedicine, Wenzhou Medical College, Wenzhou 325000, China.

PMID: 23800686
DOI: 10.1016/j.bmcl.2013.05.080

Abstract

A series of structurally novel mono-carbonyl curcumin analogues have been synthesized and biologically evaluated to test their inhibitory potencies and the structure-activity relationship (SAR) on human and rat 11β-hydroxysteroid dehydrogenase isoform (11β-HSD1) activities. 11β-HSD1 selective inhibitors have been discovered and compound A10 is discovered as a very potent with an IC50 value of 97 nM without inhibiting 11β-HSD2.

Publication types

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

MeSH terms

11-beta-Hydroxysteroid Dehydrogenase Type 1 / antagonists & inhibitors*
11-beta-Hydroxysteroid Dehydrogenase Type 1 / metabolism
11-beta-Hydroxysteroid Dehydrogenase Type 2 / antagonists & inhibitors
11-beta-Hydroxysteroid Dehydrogenase Type 2 / metabolism
Animals
Curcumin / analogs & derivatives*
Curcumin / chemical synthesis
Curcumin / metabolism
Enzyme Inhibitors / chemical synthesis*
Enzyme Inhibitors / chemistry
Enzyme Inhibitors / metabolism
Humans
Microsomes / metabolism
Protein Binding
Rats
Structure-Activity Relationship

Substances

Enzyme Inhibitors
11-beta-Hydroxysteroid Dehydrogenase Type 1
11-beta-Hydroxysteroid Dehydrogenase Type 2
Curcumin