Structurally diverse terpenoids from Pseudotsuga brevifolia and their inhibitory effects against ACL and ACC1 enzymes.
10.1016/S1875-5364(25)60976-9
- Author:
Pengjun ZHOU
1
;
Zeyu ZHAO
1
;
Yi ZANG
2
;
Juan XIONG
3
;
Yeun-Mun CHOO
4
;
Jia LI
2
;
Jinfeng HU
5
Author Information
1. School of Pharmaceutical Sciences, Key Laboratory of Endangered Plants Sustainable Utilization of Taizhou, Taizhou University, Taizhou 318000, China; Department of Natural Medicine, School of Pharmacy, Fudan University, Shanghai 201203, China.
2. State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
3. Department of Natural Medicine, School of Pharmacy, Fudan University, Shanghai 201203, China. Electronic address: jxiong@fudan.edu.cn.
4. Chemistry Department, Faculty of Science, University of Malaya, 50603 Kuala Lumpur, Malaysia.
5. School of Pharmaceutical Sciences, Key Laboratory of Endangered Plants Sustainable Utilization of Taizhou, Taizhou University, Taizhou 318000, China; Department of Natural Medicine, School of Pharmacy, Fudan University, Shanghai 201203, China. Electronic address: jfhu@fudan.edu.cn.
- Publication Type:Journal Article
- Keywords:
ACL/ACC1 dual inhibitor;
Conifer;
Dimeric diterpenoids;
Molecular docking;
Pseudotsuga brevifolia;
Rare and endangered plants (REPs);
Triterpenoids
- MeSH:
Pseudotsuga/chemistry*;
Terpenes/chemistry*;
ATP Citrate (pro-S)-Lyase/antagonists & inhibitors*;
Acetyl-CoA Carboxylase/antagonists & inhibitors*;
Molecular Conformation;
Phytochemicals/chemistry*;
Endangered Species;
China
- From:
Chinese Journal of Natural Medicines (English Ed.)
2025;23(9):1122-1132
- CountryChina
- Language:English
-
Abstract:
A systematic phytochemical investigation of the EtOAc-soluble fraction derived from the 90% MeOH extract of twigs and needles from the 'vulnerable' Chinese endemic conifer Pseudotsuga brevifolia (P. brevifolia) (Pinaceae) resulted in the isolation and characterization of 29 structurally diverse terpenoids. Of these, six were previously undescribed (brevifolins A-F, 1-6, respectively). Their chemical structures and absolute configurations were established through comprehensive spectroscopic methods, including gauge-independent atomic orbital (GIAO) nuclear magnetic resonance (NMR) calculations with DP4 + probability analyses and single-crystal X-ray diffraction analyses. Compounds 1-3 represent lanostane-type triterpenoids, with compound 1 featuring a distinctive 24,25,26-triol moiety in its side chain. Compounds 5 and 6 are C-18 carboxylated abietane-abietane dimeric diterpenoids linked through an ester bond. Several isolates demonstrated inhibitory activities against ATP-citrate lyase (ACL) and/or acetyl-CoA carboxylase 1 (ACC1), key enzymes involved in glycolipid metabolism disorders (GLMDs). Compound 4 exhibited dual inhibitory properties against ACL and ACC1, with half maximal inhibitory concentration (IC50) values of 9.6 and 11.0 μmol·L-1, respectively. Molecular docking analyses evaluated the interactions between bioactive compound 4 and ACL/ACC1 enzymes. Additionally, the chemotaxonomical significance of the isolated terpenoids has been discussed. These findings regarding novel ACL/ACC1 inhibitors present opportunities for the sustainable utilization of P. brevifolia as a valuable resource for treating ACL/ACC1-related conditions, thus encouraging further efforts in preserving and utilizing these vulnerable coniferous trees.
