Drechmerin H, a novel 1(2), 2(18)-diseco indole diterpenoid from the fungus Drechmeria sp. as a natural agonist of human pregnane X receptor

• Published in: Bioorganic chemistry Vol. 79; pp. 250 - 256
• Main Authors: Zhao, Jian-Chao, Luan, Zhi-Lin, Liang, Jia-Hao, Cheng, Zhong-Bin, Sun, Cheng-Peng, Wang, Ya-Li, Zhang, Meng-Yue, Zhang, Tian-Yuan, Wang, Yong, Yang, Tian-Mei, Wu, Ying-Ying, Zhang, Yi-Xuan, Zhao, Xin-Yu, Ma, Xiao-Chi
• Format: Journal Article
• Language: English
• Published: SAN DIEGO Elsevier Inc 01.09.2018; Elsevier
• Subjects: Agonistic effect; Biochemistry & Molecular Biology; Biological Products - chemistry; Biological Products - isolation & purification; Biological Products - pharmacology; Chemistry; Chemistry, Organic; Dose-Response Relationship, Drug; Drechmeria sp; Hep G2 Cells; Humans; Hypocreales - chemistry; Indole diterpenoid; Life Sciences & Biomedicine; Molecular docking; Molecular Structure; Physical Sciences; Pregnane X receptor; Pregnane X Receptor - agonists; Science & Technology; Structure-Activity Relationship; Indole diterpenoid; Pregnane X receptor; Drechmeria sp; Agonistic effect; Molecular docking; NODULISPORIC ACID; PHYSALIS-ANGULATA; PENICILLIUM-CRUSTOSUM; CHEMICAL DIVERSITY; ALISMA ORIENTALE; METABOLISM; SKELETON
• ISSN: 0045-2068; 1090-2120; 1090-2120
• DOI: 10.1016/j.bioorg.2018.05.001

A novel 1(2), 2(18)-diseco indole diterpenoid, drechmerin H (1), was isolated from the fermentation broth of Drechmeria sp. Compound 1 displayed the significant agonistic effect on PXR with EC50 value of 134.91 nM. [Display omitted] •A novel 1(2), 2(18)-diseco indole diterpenoid 1 was isolated from the fermentation broth of Drechmeria sp.•Compounds 1–3 were assayed for their agonistic effects against PXR.•Compound 1 displayed the significant agonistic effect against PXR with EC50 value of 134.91 nM.•Molecular docking revealed interaction of compound 1 with PXR. A novel 1(2), 2(18)-diseco indole diterpenoid, drechmerin H (1), was isolated from the fermentation broth of Drechmeria sp. together with a new indole diterpenoid, 2′-epi terpendole A (3), and a known analogue, terpendole A (2). Their structures were determined by HRESIMS, 1D and 2D NMR, ECD, and X-ray single crystal diffraction analyses as well as quantum chemical calculation. The abosulte configuration of terpendole A (2) was determined for the first time. Compound 1 displayed the significant agonistic effect on pregnane X receptor (PXR) with EC50 value of 134.91 ± 2.01 nM, and its interaction with PXR was investigated by molecular docking. Meantime, a plausible biosynthetic pathway for compounds 1–3 is also discussed in the present work.