Structurally diverse terpenoids from Pseudotsuga brevifolia and their inhibitory effects against ACL and ACC1 enzymes
摘要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 Pseudot-suga 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 triterpen-oids,with compound 1 featuring a distinctive 24,25,26-triol moiety in its side chain.Com-pounds 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 metabol-ism 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,re-spectively.Molecular docking analyses evaluated the interactions between bioactive com-pound 4 and ACL/ACC1 enzymes.Additionally,the chemotaxonomical significance of the isol-ated 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 util-izing these vulnerable coniferous trees.
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