Brasilterpenes A-E, Bergamotane Sesquiterpenoid Derivatives with Hypoglycemic Activity from the Deep Sea-Derived Fungus Paraconiothyrium brasiliense HDN15-135

Wenxue Wang; Yeqin Shi; Yuanyuan Liu; Yundong Zhang; Jiajin Wu; Guojian Zhang; Qian Che; Tianjiao Zhu; Mingyu Li; Dehai Li

doi:10.3390/md20050338

Brasilterpenes A-E, Bergamotane Sesquiterpenoid Derivatives with Hypoglycemic Activity from the Deep Sea-Derived Fungus Paraconiothyrium brasiliense HDN15-135

Mar Drugs. 2022 May 23;20(5):338. doi: 10.3390/md20050338.

Authors

Wenxue Wang¹, Yeqin Shi², Yuanyuan Liu¹, Yundong Zhang¹, Jiajin Wu¹, Guojian Zhang^{1

3}, Qian Che¹, Tianjiao Zhu¹, Mingyu Li², Dehai Li^{1

3}

Affiliations

¹ Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China.
² Fujian Provincial Key Laboratory of Innovative Drug Target Research, School of Pharmaceutical Science, Xiamen University, Xiamen 361102, China.
³ Laboratory for Marine Drugs and Bioproducts of Qingdao National Laboratory for Marine Science and Technology, Qingdao 266237, China.

Abstract

Five bergamotane sesquiterpenoid derivatives, brasilterpenes A-E (1-5), bearing an unreported spiral 6/4/5 tricyclic ring system, were isolated from the deep sea-derived ascomycete fungus Paraconiothyrium brasiliense HDN15-135. Their structures, including absolute configurations, were established by extensive spectroscopic methods complemented by single-crystal X-ray diffraction analyses, electronic circular dichroism (ECD), and density-functional theory (DFT) calculations of nuclear magnetic resonance (NMR) data including DP4+ analysis. The hypoglycemic activity of these compounds was assessed using a diabetic zebrafish model. Brasilterpenes A (1) and C (3) significantly reduced free blood glucose in hyperglycemic zebrafish in vivo by improving insulin sensitivity and suppressing gluconeogenesis. Moreover, the hypoglycemic activity of compound 3 was comparable to the positive control, anti-diabetes drug rosiglitazone. These results suggested brasilterpene C (3) had promising anti-diabetes potential.

Keywords: ascomycete fungus Paraconiothyrium brasiliense; bergamotane sesquiterpenoids; hypoglycemic activity; marine-derived fungus.

MeSH terms

Animals
Ascomycota* / chemistry
Hypoglycemic Agents / pharmacology
Sesquiterpenes* / chemistry
Zebrafish

Substances

Hypoglycemic Agents
Sesquiterpenes

Supplementary concepts

Paraconiothyrium brasiliense

Grants and funding

This work was financially supported by the Major national science and technology projects of the Ministry of science and technology (81991522), the Key Laboratory of Marine Biotechnology of Fujian Province (2021MB02), National Science and Technology Major Project for Significant New Drugs Development (2018ZX09735004), Major Basic Research Programs of Natural Science Foundation of Shandong Province (ZR2019ZD18, ZR2021ZD28), Taishan Scholar Youth Expert Program in Shandong Province (No. tsqn201812021), the Pilot National Laboratory for Marine Science and Technology (LMDBKF201805), and the Fundamental Research Funds for the Central Universities (No. 201941001, 2019KJM004, 202172002).