Hyperkouytones A—O,New Polyprenylated Acylphloroglucinols from Hypericum kouytchense with Multidrug Resistance Reversal Activity  

作　　者：Hua-Yong Lou Mei-Jun Chen Ping Yi Jun Jin Yan-Rong Zeng Wei Gu Zhan-Xing Hu Jue Yang Xiao-Jiang Hao Chun-Mao Yuan 

机构地区：[1]State Key Laboratory of Functions and Applications of Medicinal Plants,Guizhou Medical University,Guiyang,Guizhou 550014,China [2]Natural Products Research Center,Guiyang,Guizhou,550014 China [3]School of Pharmaceutical Sciences,Guizhou Medical University,Guiyang,Guizhou 561113,China [4]State Key Laboratory of Phytochemistry and Plant Resources in West China,Kunming Institute of Botany,Kunming,Yunnan 650201,China

出　　处：《Chinese Journal of Chemistry》2024年第24期3293-3307,共15页中国化学(英文版)

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);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.

摘　　要：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.

关 键 词：Natural products Hypericum kouytchense PHYTOCHEMISTRY Structure elucidation Multidrug resistance reversal activity 

分 类 号：R73[医药卫生—肿瘤]