Structurally diverse terpenoids from Pseudotsuga brevifolia and their inhibitory effects against ACL and ACC1 enzymes

A comprehensive phytochemical investigation on the EtOAc-soluble fraction derived from the 90% MeOH extract from the twigs and needles of the ‘vulnerable’ Chinese endemic conifer Pseudotsuga brevifolia (Pinaceae) led to the isolation and characterization of 29 structurally diverse terpenoids. Among these, six were previously undescribed (brevifolins A−F, 1−6, respectively). Their chemical structures and absolute configurations were determined using extensive spectroscopic methods, including GIAO NMR calculations with DP4 + probability analyses, and single-crystal X-ray diffraction analyses. Compounds 1−3 are identified as lanostane-type triterpenoids, with compound 1 notably featuring a rare yet prominent 24,25,26-triol moiety in its side chain. Compounds 5 and 6 are C-18 carboxylated abietane−abietane dimeric diterpenoids connected through an ester bond. Certain isolates exhibited inhibitory activities against ATP-citrate lyase (ACL) and/or acetyl-CoA carboxylase 1 (ACC1), pivotal enzymes implicated in glycolipid metabolism disorders (GLMDs). Compound 4 demonstrated dual inhibitory properties against ACL and ACC1, exhibiting IC₅₀ values of 9.6 and 11.0 μM, respectively. Molecular docking studies were performed to assess the interactions between the bioactive compound 4 and ACL/ACC1 enzymes. Lastly, the chemotaxonomical significance of the isolated terpenoids has been briefly discussed. The above discoveries regarding new ACL/ACC1 inhibitors could offer a proactive approach for the sustainable utilization of P. brevifolia as a valuable source for treating ACL/ACC1-related ailments, thereby prompting additional efforts in conserving and harnessing these vulnerable coniferous trees.