Conformational analysis of an anti-androgenic, (E,E)-8-hydroxygermacrene B, using NOESY and dynamic NMR spectroscopy

Jukkarin Srivilai; Nantaka Khorana; Neti Waranuch; Nungruthai Suphrom; Kornkanok Ingkaninan

doi:10.1016/j.bmcl.2014.05.057

Conformational analysis of an anti-androgenic, (E,E)-8-hydroxygermacrene B, using NOESY and dynamic NMR spectroscopy

Bioorg Med Chem Lett. 2014 Aug 1;24(15):3526-9. doi: 10.1016/j.bmcl.2014.05.057. Epub 2014 May 27.

Authors

Jukkarin Srivilai¹, Nantaka Khorana², Neti Waranuch³, Nungruthai Suphrom⁴, Kornkanok Ingkaninan⁵

Affiliations

¹ Bioscreening Unit, Department of Pharmaceutical Chemistry and Pharmacognosy, Faculty of Pharmaceutical Sciences and Center of Excellence for Innovation in Chemistry, Naresuan University, Phitsanulok 65000, Thailand.
² Department of Pharmaceutical Chemistry and Pharmacognosy, Faculty of Pharmaceutical Sciences and Center of Excellence for Innovation in Chemistry, Naresuan University, Phitsanulok 65000, Thailand.
³ Department of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences and Center of Excellence for Innovation in Chemistry, Naresuan University, Phitsanulok 65000, Thailand.
⁴ Department of Chemistry, Faculty of Science, Naresuan University, Phitsanulok 65000, Thailand.
⁵ Bioscreening Unit, Department of Pharmaceutical Chemistry and Pharmacognosy, Faculty of Pharmaceutical Sciences and Center of Excellence for Innovation in Chemistry, Naresuan University, Phitsanulok 65000, Thailand. Electronic address: k_ingkaninan@yahoo.com.

PMID: 24951332
DOI: 10.1016/j.bmcl.2014.05.057

Abstract

(E,E)-8-Hydroxygermacrene B was prepared by ketone reduction of germacrone, a naturally occurring compound from Curcuma aeruginosa Roxb. with NaBH4 at low temperature (4 °C). This compound showed remarkable in vitro anti-androgenic activity (IC50 0.15±0.022 mM) applicable to male baldness treatments. NMR analysis at -50 °C indicated that there were four conformational isomers of (E,E)-8-hydroxygermacrene B in a ratio of 48:40:8:4. The major conformers were assigned by (1)H NMR and 2D-NOESY NMR spectroscopy as having methyl groups at C-10 and C-4 in up-down (UD) orientations (48% predominance) and UU (40%). (1)H NMR spectra implied another two minor conformers with these methyls having DU (8%) and DD (4%) orientations.

Keywords: (E,E)-8-Hydroxygermacrene B; Anti-androgen; Conformational analysis; Dynamic NMR spectroscopy; Sesquiterpenoids.

Publication types

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

MeSH terms

Androgen Antagonists / chemistry*
Curcuma / chemistry
Magnetic Resonance Spectroscopy / standards
Molecular Conformation
Reference Standards
Rhizome / chemistry
Sesquiterpenes, Germacrane / chemistry*

Substances

8-hydroxygermacrene B
Androgen Antagonists
Sesquiterpenes, Germacrane