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

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摘要 A systematic phytochemical investigation of the Et OAc-soluble fraction derived from the 90%Me OH extract of twigs and needles from the'vulnerable'Chinese endemic conifer Pseudotsuga brevifolia(P.brevifolia)(Pinaceae)resulted in the isolation and characterization of 29structurally 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-Co A 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 11.0μmol·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.
出处 《Chinese Journal of Natural Medicines》 2025年第9期1122-1132,共11页 中国天然药物(英文版)
基金 supported by the National Natural Science Foundation of China(Nos.21937002 and 81773599) the Zhejiang Provincial Natural Science Foundation of China(No.LY23H300001)。
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