In Vtro Anti-Androgen Activity of Germacrone Analogs

Name: Jukkarin Srivilai

keyword: Germacrone

LCSH: Antiandrogens -- Research

; Curcuma aeruginosa

LCSH: Hormones, -- Sex -- Therapeutic -- use

; Anti-androgen

; 5-Alpha reductase inhibitor

; Sesquiterpenes

Abstract: The $5\alpha$-reductase enzyme plays a critical role in the development of various androgen-dependent conditions, including androgenic alopecia, benign prostatic hyperplasia (BPH), hirsutism, prostate cancer, and acne. Consequently, inhibitors of this enzyme are highly sought after for therapeutic applications. Previous studies, both in vitro and in vivo, have identified that the extract from Curcuma aeruginosa Roxb. and its primary sesquiterpenoid component, germacrone (1), possess potent inhibitory effects on $5\alpha$-reductase. This research aimed to further investigate the structure-activity relationships (SAR) of germacrone and its related analogs regarding their anti-androgenic potential.In this study, three major sesquiterpenes—germacrone (1), furanodiene (2), and germacrene B (3)—were successfully isolated from the hexane extract of C. aeruginosa rhizomes. Using compounds 1 and 2 as precursor materials, seven additional germacrone analogs (4-9) were synthesized through a series of chemical transformations, including ring pyrolysis, ketone reduction, acetylation, and methylation. The chemical structures of all synthesized compounds were rigorously characterized and confirmed.The anti-androgenic activity was evaluated based on the percentage of enzymatic inhibition. Among the nine compounds tested, germacrone (1), 8-hydroxygermacrene B (4), and elemenol (6) exhibited the most significant activity, each achieving over 60% inhibition at a concentration of 1 mg/mL. Notably, compound 4 (8-hydroxygermacrene B) demonstrated higher potency than the parent compound, germacrone. The SAR analysis revealed that the $\alpha,\beta$-unsaturated alcohol moiety at the C-8 position is a pivotal functional group for the inhibition of the $5\alpha$-reductase enzyme. In contrast, modifications such as 8-alkoxyl substitution on compound 4 or structural changes via pyrolysis did not lead to an improvement in inhibitory efficacy.In conclusion, these findings identify sesquiterpenoid compounds 4 and 6 as promising lead candidates for the further design and development of novel anti-androgenic pharmacological agents.

NARESUAN UNIVERSITY. NARESUAN UNIVERSITY LIBRARY

Address: PHITSANULOK

Email: library@nu.ac.th

Name: Kornkanok Ingkaninan

Role: Advisor

Created: 2569

Modified: 2026-05-02

Issued: 2026-05-02

วิทยานิพนธ์/Thesis

application/pdf

eng

DegreeName: Master of Science

Level: Master's degree

Descipline: Pharmaceutical Chemistry and Natural Products

Grantor: Naresuan University

©copyrights Naresuan University

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