Anti-Diabetic Indole-Terpenoids From Penicillium sp. HFF16 Isolated From the Rhizosphere Soil of Cynanchum bungei Decne

Abstract

Finding novel anti-diabetic compounds with effective suppression activities against hepatic glucagon response is urgently required for the development of new drugs against diabetes. Fungi are well known for their ability to produce new bioactive secondary metabolites. As part of our ongoing research, five new indole-terpenoids (1–5), named encindolenes D-H, were isolated from the fungus Penicillium sp. HFF16 from the rhizosphere soil of Cynanchum bungei Decne. The structures of the compounds were elucidated by spectroscopic data and ECD analysis. In the anti-diabetic activity assay, compounds 1–5 could inhibit the hepatic glucose production with EC50 values of 17.6, 30.1, 21.3, 9.6, and 9.9 μM, respectively, and decrease the cAMP contents in glucagon-induced HepG2 cells.

The Novel Compounds with Biological Activity Derived from Soil Fungi in the Past Decade

“… [ 6 ] 204 Aspergorakhin C 205 Aspergorakhin D 206* Encindolene D Penicillium sp . HFF16 Rhizosphere soil of Cynanchum bungei Decne., in Mount Tai, China Inhibit the hepatic glucose production(206*, 207*, 208*, 209*, 210*) [ 74 ] 207* Encindolene E 208* Encindolene F 209* Encindolene G 210* Encindolene H 211* 4 α -methyl-9 α -methoxyandrosta-8,15-diene-3,17-dione Curvularia borreriae strain HS-FG-237 - Cytotoxicity; anti-inflammatory activity [ 75 ] 212* Unnamed Aspergillus flavus JDW-1 - Cytotoxicity [ 76 ] 213* Aspergorakhin A Aspergillus gorakhpurensis F07ZB1707 Mountainous region of Shennongjia Forestry District, Hubei Province of China Inhibitory effect against Protein tyrosine phosphatases including PTP1B, SHP1, and TCPTP in vitro. [ 6 ] Ketones 214* 1-(3,5-dihydroxyphenyl)-4-hydroxypentan-2-one Exophiala pisciphila PHF-9 Yunnan Province, China, Cytotoxicity [ 77 ] 215* Pyrenocine J Curvularia affifinis strain HS-FG-196 …”

“… 150 Compounds 206 – 210 could inhibit the hepatic glucose production with EC 50 values of 17.6, 30.1, 21.3, 9.6, and 9.9 μM, respectively, and decrease the cAMP contents in glucagon-induced HepG2 cells. 74 …”

Prenylated indole-terpenoids with antidiabetic activities from Penicillium sp. HFF16 from the rhizosphere soil of Cynanchum bungei Decne

“…These results also suggested that the absolute configurations of all the chiral carbon except for C-18 in 1, 2, and 5 were the same. Until now, a total of 17 indole-terpenoids including compounds 1-5 and other twelve previously reported analogs such as encindolenes A-C, 18-O-methyl-encindolene A , encindolenes D-H (Xiao et al, 2022), paspalitrem C (Dorner et al, 1984), 7-methoxypaxilline (Ariantari et al, 2019), and 7-hydroxy-13dehydroxypaxilline (Peter and Christopher, 1994) have been identified from Penicillium sp. HFF16, and the plausible biosynthetic pathway of the eight different skeletons was shown in Scheme 2.…”

“…In our preliminary search for bioactive metabolites from Penicillium sp. HFF16, from the rhizosphere soil of Cynanchum bungei Decne from Mount Tai, China, nine new indoleterpenoids with weak anti-inflammatory activities and antidiabetic effects were investigated Xiao et al, 2022).…”