Structurally Diverse Triterpene-26-oic Acids as Potential Dual ACL and ACC1 Inhibitors from the Vulnerable Conifer Keteleeria fortunei.
J Nat Prod
; 86(6): 1487-1499, 2023 06 23.
Article
en En
| MEDLINE
| ID: mdl-37291059
ABSTRACT
A preliminary phytochemical investigation on the 90% MeOH extract from the twigs and needles of the vulnerable conifer Keteleeria fortunei led to the isolation and characterization of 17 structurally diverse triterpen-26-oic acids, including nine previously undescribed ones (fortunefuroic acids A-I, 1-9) featuring a rare furoic acid moiety in the lateral chain. Among them, 1-5 are uncommon 9ßH-lanostane-type triterpenoic acids. Friedo-rearranged triterpenoids 6 and 7 feature a unique 17,14-friedo-lanostane skeleton, whereas 9 possesses a rare 17,13-friedo-cycloartane-type framework. Their structures and absolute configurations were elucidated by extensive spectroscopic (e.g., detailed 2D NMR) and computational (NMR/ECD) calculations and the modified Mosher's method. In addition, the absolute structure of compound 1 was ascertained by single-crystal X-ray diffraction analyses. Fortunefuroic acids B (2), G (7), and I (9), along with isomangiferolic acid (12) and 3α,27-dihydroxycycloart-24E-en-26-oic acid (14), exhibited dual inhibitory effects against the adenosine triphosphate (ATP)-citrate lyase (ACL, IC50s 5.7-11.4 µM) and acetyl-CoA carboxylase 1 (ACC1, IC50s 7.5-10.5 µM), both of which are key enzymes for glycolipid metabolism. The interactions of the bioactive triterpenoids with both enzymes were examined by molecular docking studies. The above findings reveal the important role of protecting plant species diversity in support of chemical diversity and potential sources of new therapeutics for ACL-/ACC1-associated diseases.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Triterpenos
/
Abies
/
Tracheophyta
Idioma:
En
Revista:
J Nat Prod
Año:
2023
Tipo del documento:
Article