Fortunefuroic Acid J from Keteleeria Hainanensis and its Dual Inhibitory Effects on ATP-Citrate Lyase and Acetyl-CoA Carboxylase
Document Type
Article
Publication Date
12-1-2024
Abstract
A previously undescribed triterpenoid (fortunefuroic acid J, 1) was isolated from the endangered conifer Keteleeria hainanensis, along with 20 other known terpenoids. Compound 1 is characterized by an unusual 3,4-seco-9 beta H-lanost-3-oic acid motif, featuring a rare furoic acid moiety in its lateral chain. The structure elucidation of this compound was achieved through a combination of spectroscopic and computational methods. The C-15 epimers of 15-methoxypinusolidic acid (15R-8 and 15S-9) were successfully separated and identified for the first time. Compound 1 demonstrated dual inhibitory effects against ATP-citrate lyase (ACL, IC50: 0.92 mu M) and acetyl-CoA carboxylase 1 (ACC1, IC50: 10.76 mu M). Compounds 2 and 11 exclusively inhibited ACL, exhibiting IC50 values of 2.64 and 6.35 mu M, respectively. Compound 1 is classified among the fortunefuroic acid-type compounds, previously isolated from K. fortunei, distinguished by the presence of a rare furoic acid moiety in their lateral chain. The chemotaxonomic significance of the 9 beta H-lanost-26-oic acids in Keteleeria was briefly discussed. These findings highlight the importance of conserving plant species diversity, thereby enhancing the exploration of structurally diverse compounds and potential avenues for developing new therapeutics targeting ACL/ACC1-associated diseases.
Keywords
Keteleeria hainanensis, Pinaceae, Fortunefuroic acid, ATP-citrate lyase, Acetyl-CoA carboxylase 1, Natural products, Terpenoids
Divisions
CHEMISTRY
Funders
National Natural Science Foundation of China (NSFC) (21937002) ; (81773599),Natural Science Foundation of Zhejiang Province (LY23H300001)
Publication Title
Chemistry & Biodiversity
Volume
21
Issue
12
Publisher
Wiley
Publisher Location
POSTFACH 101161, 69451 WEINHEIM, GERMANY