Xiong, Juan and Zhou, Peng-Jun and Jiang, Hao-Wen and Huang, Ting and He, Yu-Hang and Zhao, Ze-Yu and Zang, Yi and Choo, Yeun-Mun and Wang, Xiaojuan and Chittiboyina, Amar G. and Pandey, Pankaj and Hamann, Mark T. and Li, Jia and Hu, Jin-Feng (2021) Forrestiacids A and B, pentaterpene inhibitors of ACL and lipogenesis: Extending the limits of computational NMR methods in the structure assignment of complex natural products. Angewandte Chemie-International Edition, 60 (41). pp. 22270-22275. ISSN 1433-7851, DOI https://doi.org/10.1002/anie.202109082.
Full text not available from this repository.Abstract
Forrestiacids A (1) and B (2) are a novel class of 4+2] type pentaterpenoids derived from a rearranged lanostane moiety (dienophile) and an abietane unit (diene). These unprecedented molecules were isolated using guidance by molecular ion networking (MoIN) from Pseudotsuga forrestii, an endangered member of the Asian Douglas Fir Family. The intermolecular hetero-Diels-Alder adducts feature an unusual bicyclo2.2.2]octene ring system. Their structures were elucidated by spectroscopic analysis, GIAO NMR calculations and DP4+ probability analyses, electronic circular dichroism calculations, and X-ray diffraction analysis. This unique addition to the pentaterpene family represents the largest and the most complex molecule successfully assigned using computational approaches to predict accurately chemical shift values. Compounds 1 and 2 exhibited potent inhibitory activities (IC(50)s mu M) of ATP-citrate lyase (ACL), a new drug target for the treatment of glycolipid metabolic disorders including hyperlipidemia. Validating this activity 1 effectively attenuated the de novo lipogenesis in HepG2 cells. These findings provide a new chemical class for developing potential therapeutic agents for ACL-related diseases with strong links to traditional medicines.
| Item Type: | Article |
|---|---|
| Funders: | National Natural Science Foundation of China (NSFC)[21937002] |
| Uncontrolled Keywords: | Forrestiacids;Lipogenesis inhibitors;Natural products; Structure elucidation;Terpenoids |
| Subjects: | Q Science > QD Chemistry |
| Divisions: | Faculty of Science |
| Depositing User: | Ms Zaharah Ramly |
| Date Deposited: | 13 Jun 2022 02:50 |
| Last Modified: | 13 Jun 2022 02:50 |
| URI: | http://eprints.um.edu.my/id/eprint/34581 |
Actions (login required)
 |
View Item |
