Discovery of Polycyclic Polyprenylated Acylphloroglucinols from Hypericum androsaemum as Dual-Mechanism Inhibitors of Mycobacterium tuberculosis GlmU Acetyltransferase.

Authors

Jiangchun Wei, Xingpiao Jin, Xiangwang Zhao, Pingping Fan, Ning Wang, Siyu Chen, Yan Li, Jinsheng Wang, Yonghui Zhang, Zhengxi Hu

Published in

Organic letters. Volume 28. Issue 32. Pages 10296-10301. Aug 14, 2026.

Abstract

(±)-Hypericandrone A (HCA, 1), an unprecedented pair of enantiomeric polycyclic polyprenylated acylphloroglucinols (PPAPs), and its biosynthetic congener hypericandrone B (HCB, 2) were isolated from the fruits of Hypericum androsaemum. Compound 1 features a unique 2-cyclopentane-bicyclo[3.3.0]octane scaffold, while 2 possesses a rare 2-cyclopentyltetrahydrofuran framework. Their absolute configurations were unequivocally determined by spectroscopic analysis, single-crystal X-ray diffraction, and ECD calculations. Remarkably, (+)-1 displayed potent antitubercular activity by selectively inhibiting the acetyltransferase domain of Mycobacterium tuberculosis GlmU through a dual mechanism, acting competitively against acetyl-CoA (Ki = 0.07 μM) and noncompetitively against glucosamine-1-phosphate (GlcN-1-P, Ki = 0.20 μM).

PMID:
42599433
Bibliographic data and abstract were imported from PubMed on 15 Aug 2026.

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