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

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

JOURNAL=Frontiers in Chemistry

VOLUME=9

YEAR=2021

URL=https://www.frontiersin.org/journals/chemistry/articles/10.3389/fchem.2021.797858

DOI=10.3389/fchem.2021.797858

ISSN=2296-2646

ABSTRACT=<p>Three new humulane-type sesquiterpenoids, penirolide A (<bold>1</bold>), penirolide B (<bold>2</bold>), and 10-acetyl-phomanoxide (<bold>3</bold>), together with three known compounds aurasperone A (<bold>4</bold>), pughiinin A (<bold>5</bold>), and cyclo(<sc>l</sc>-Leu-<sc>l</sc>-Phe) (<bold>6</bold>) were isolated from the endophytic fungus <italic>Penicillium</italic> sp<italic>.</italic> derived from the leaves of <italic>Carica papaya</italic> 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 <bold>2</bold>, <bold>3</bold>, <bold>5</bold>, and <bold>6</bold> significantly inhibited glucagon-induced hepatic glucose production, with EC<sub>50</sub> values of 33.3, 36.1, 18.8, and 32.1 μM, respectively. Further study revealed that compounds <bold>2</bold>, <bold>3</bold>, <bold>5</bold>, and <bold>6</bold> inhibited hepatic glucose production by suppression of glucagon-induced cAMP accumulation.</p>