Eleven biogenetically related polyprenylated acylphloroglucinols(PPAPs),including four novel skeletons(1-4)and five new com-pounds(5-9),were isolated from the flowers of Hypericum monogynum.Hypermonones A-D(1-4)repres...Eleven biogenetically related polyprenylated acylphloroglucinols(PPAPs),including four novel skeletons(1-4)and five new com-pounds(5-9),were isolated from the flowers of Hypericum monogynum.Hypermonones A-D(1-4)represented the first example of a unique dilactone structure containing carbonyl bonded single 5-lactone and tricyclic γ-lactone moieties.Their structures were elucidated by NMR analysis,X-ray crystallography,and ECD calculations.Moreover,we revised the structure of hyperibrin B to hy perm on one I(9)via NMR an alysis,a qua ntum computational chemistry method,and hypothetic bios yn thetic con siderations.Three compounds(5,6,and 9)with significant MDR reversal activity(RF ranging from 61 to 223)were superior to the positive control verapamil(MCF-7/ADR,RF:53;HepG2/ADRz RF:124).Mechanism study for compound 5 indicated that this compound could inhibit the function of P-gp tran sport rather tha n its expressi on,and the possible recog nition mechanism betwee n compo und 5 and P-gp was predicted by molecular docking.展开更多
Given the lack of systematic polyprenylated acylphloroglucinols(PPAPs)research on traditional Chinese medicine of Hypericum kouytchense,this plant was applied for the phytochemical study,which led to fifteen new PPAP...Given the lack of systematic polyprenylated acylphloroglucinols(PPAPs)research on traditional Chinese medicine of Hypericum kouytchense,this plant was applied for the phytochemical study,which led to fifteen new PPAPs(1—15,PPAPs),along with 36 known PPAP derivatives.Their structures and absolute configurations were established by comprehensive spectral analysis and theoretical ECD and NMR calculations.Structurally,compound 1 possesses a rare fused 6/6/6/5/5 pentacyclic ring system.Eleven compounds exhibited good multidrug resistance reversal activity(RF ranging from 5 to 53)in HepG2/ADR cells.Importantly,compound 34,the most potential MDR modulator,showed better reversal effect(RF:53)than positive control,verapamil.The primary mechanistic study of compound 34,implied that this compound could prohibit the function of P-gp transport rather than its expression.The possible recognition mechanism between compound 34 and P-gp was predicted by molecular docking.展开更多
基金supported by the National Natural Science Foundation of China(Nos.U1812403,81872772,and 81960546)the Scie nee and Tech no logy Departme nt of Guizhou Province(Nos.QKH 2020-1Z076,QKHZC[2020]4Y203z QKHJC[2018]1409,QKHZC[2019]2762,and QKHPTRC[2020]5008)+3 种基金the High-level Innovative Talents in Guizhou Provinee(Thousand Levels of Talent for Chunmao Yuan in 2018)the"Light of the West"Talent Cultivation Program of Chinese Academy of Sciences for Chunmao Yuan(No.RZ[2020]82)the 100 Leading Talents of Guizhou Provinee(fund for Y.M.L)the Guizhou Provincial Engineering Research Center for Natural Drugs.
文摘Eleven biogenetically related polyprenylated acylphloroglucinols(PPAPs),including four novel skeletons(1-4)and five new com-pounds(5-9),were isolated from the flowers of Hypericum monogynum.Hypermonones A-D(1-4)represented the first example of a unique dilactone structure containing carbonyl bonded single 5-lactone and tricyclic γ-lactone moieties.Their structures were elucidated by NMR analysis,X-ray crystallography,and ECD calculations.Moreover,we revised the structure of hyperibrin B to hy perm on one I(9)via NMR an alysis,a qua ntum computational chemistry method,and hypothetic bios yn thetic con siderations.Three compounds(5,6,and 9)with significant MDR reversal activity(RF ranging from 61 to 223)were superior to the positive control verapamil(MCF-7/ADR,RF:53;HepG2/ADRz RF:124).Mechanism study for compound 5 indicated that this compound could inhibit the function of P-gp tran sport rather tha n its expressi on,and the possible recog nition mechanism betwee n compo und 5 and P-gp was predicted by molecular docking.
基金supported by the National Natural Science Foundation of China(Nos.32270413,82060631,and 82304348)the Science and Technology Department of Guizhou Province(No.QKHJC-ZK[2023]YB156)+6 种基金Excellent Young Talents Plan of Guizhou Medical University(2023,No.106)the 13th batch of outstanding young scientific and technological talents in Guizhou Province(No.QKHPTRC[2021]5633)Guizhou Science and Technology Innovation Talent Team(No.QKHPTRCCXTD[2022j007)High-level Innovative Talents in Guizhou Province(Thousand Levels of Talent for Chunmao Yuan in 2018)Guiyang Science and Technology Talent Training Project([2023]48-5)the project of State Key Laboratory of Functions and Applications of Medicinal Plants,GuizhouMedical University(No.QJJ[2023]113)Guizhou Provincial Engineering Research CenterforNatural Drugs.
文摘Given the lack of systematic polyprenylated acylphloroglucinols(PPAPs)research on traditional Chinese medicine of Hypericum kouytchense,this plant was applied for the phytochemical study,which led to fifteen new PPAPs(1—15,PPAPs),along with 36 known PPAP derivatives.Their structures and absolute configurations were established by comprehensive spectral analysis and theoretical ECD and NMR calculations.Structurally,compound 1 possesses a rare fused 6/6/6/5/5 pentacyclic ring system.Eleven compounds exhibited good multidrug resistance reversal activity(RF ranging from 5 to 53)in HepG2/ADR cells.Importantly,compound 34,the most potential MDR modulator,showed better reversal effect(RF:53)than positive control,verapamil.The primary mechanistic study of compound 34,implied that this compound could prohibit the function of P-gp transport rather than its expression.The possible recognition mechanism between compound 34 and P-gp was predicted by molecular docking.
