Bis-Iridoid Glycosides and Triterpenoids from and Their Potential As Inhibitors of ACC1 and ACL

Overview

Journal Molecules

Publisher MDPI

Specialty Biology

Date 2025 Jan 8

PMID 39770069

Authors

Jiang Wan

Ze-Yu Zhao

Can Wang

Chun-Xiao Jiang

Ying-Peng Tong

Yi Zang

Yeun-Mun Choo

Jia Li

Jin-Feng Hu

Affiliations

Soon will be listed here.

Abstract

A comprehensive phytochemical investigation of the twigs/leaves and flower buds of , a rare deciduous shrub native to China, led to the isolation of 39 structurally diverse compounds. These compounds include 11 iridoid glycosides (- and -), 20 triterpenoids (, , and -), and 8 phenylpropanoids (-). Among these, amabiliosides A () and B () represent previously undescribed bis-iridoid glycosides, while amabiliosides C () and D () feature a unique bis-iridoid-monoterpenoid indole alkaloid scaffold with a tetrahydro--carboline-5-carboxylic acid moiety. Amabiliacids A () and B () are 24-nor-ursane-type triterpenoids characterized by an uncommon ∆ transannular double bond. Their chemical structures and absolute configurations were elucidated through spectroscopic data and electronic circular dichroism analyses. Compound exhibited a moderate inhibitory effect against acetyl CoA carboxylase 1 (ACC1), with an IC value of 9.6 μM. Lonicejaposide C (), 3---caffeoyl-olean-12-en-28-oic acid (), and (23)-coumaroylhederagenin () showed notable inhibitory effects on ATP-citrate lyase (ACL), with IC values of 3.6, 1.6, and 4.7 μM, respectively. Additionally, 3-acetyl-ursolic acid () demonstrated dual inhibitory activity against both ACC1 and ACL, with IC values of 10.3 and 2.0 μM, respectively. The interactions of the active compounds with ACC1 and ACL enzymes were examined through molecular docking studies. From a chemotaxonomic perspective, the isolation of bis-iridoid glycosides in this study may aid in clarifying the taxonomic relationship between the genera and within the Caprifoliaceae family. These findings highlight the importance of conserving plant species with unique and diverse secondary metabolites, which could serve as potential sources of new therapeutic agents for treating ACC1/ACL-associated diseases.

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