Humulane-Type Macrocyclic Sesquiterpenoids From the Endophytic Fungus Penicillium sp. of Carica papaya

Fu-Run Wang; Li Yang; Fan-Dong Kong; Qing-Yun Ma; Qing-Yi Xie; You-Gen Wu; Hao-Fu Dai; Ping Chen; Na Xiao; You-Xing Zhao

doi:10.3389/fchem.2021.797858

Humulane-Type Macrocyclic Sesquiterpenoids From the Endophytic Fungus Penicillium sp. of Carica papaya

Front Chem. 2021 Dec 16:9:797858. doi: 10.3389/fchem.2021.797858. eCollection 2021.

Authors

Fu-Run Wang^{1

2}, Li Yang¹, Fan-Dong Kong³, Qing-Yun Ma¹, Qing-Yi Xie¹, You-Gen Wu², Hao-Fu Dai⁴, Ping Chen², Na Xiao⁵, You-Xing Zhao¹

Affiliations

¹ Haikou Key Laboratory for Research and Utilization of Tropical Natural Products, Institute of Tropical Bioscience and Biotechnology, CATAS, Haikou, China.
² Key Laboratory for Quality Regulation of Tropical Horticultural Crops of Hainan Province, College of Horticulture, Hainan University, Haikou, China.
³ Key Laboratory of Chemistry and Engineering of Forest Products, State Ethnic Affairs Commission, Guangxi Key Laboratory of Chemistry and Engineering of Forest Products, Guangxi Collaborative Innovation Center for Chemistry and Engineering of Forest Products, School of Chemistry and Chemical Engineering, Guangxi University for Nationalities, Nanning, China.
⁴ Hainan Institute for Tropical Agricultural Resources, CATAS, Haikou, China.
⁵ State Key Laboratory of Crop Biology, College of Agronomy, Shandong Agriculture University, Tai'an, Shandong, China.

Abstract

Three new humulane-type sesquiterpenoids, penirolide A (1), penirolide B (2), and 10-acetyl-phomanoxide (3), together with three known compounds aurasperone A (4), pughiinin A (5), and cyclo(l-Leu-l-Phe) (6) were isolated from the endophytic fungus Penicillium sp. derived from the leaves of Carica papaya L. Their structures including their absolute configurations were determined based on the analysis of NMR and HRESIMS spectra, NMR chemical shifts, and ECD calculations. Compounds 2, 3, 5, and 6 significantly inhibited glucagon-induced hepatic glucose production, with EC₅₀ values of 33.3, 36.1, 18.8, and 32.1 μM, respectively. Further study revealed that compounds 2, 3, 5, and 6 inhibited hepatic glucose production by suppression of glucagon-induced cAMP accumulation.

Keywords: Penicillium sp.; anti-diabetic activity; cAMP accumulation; endophytic fungus; humulane-type sesquiterpenoid.