Targeted isolation of antiviral cinnamoylphloroglucinol-terpene adducts from Cleistocalyx operculatus by building blocks-based molecular networking approach  

作　　者：Jianguo Song Ruili Huang Jialiao Cai Zhenlong Wu Lijun Hu Wanyang Sun Xiaojun Huang Rongrong He Wei Tang Wencai Ye Ying Wang 

机构地区：[1]State Key Laboratory of Bioactive Molecules and Druggability Assessment,Jinan University,Guangzhou 510632,China [2]Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM&New Drugs Research,Jinan University,Guangzhou 510632,China [3]Guangdong-Hong Kong-Macao Joint Laboratory for Pharmacodynamic Constituents of TCM and New Drugs Research,Jinan University,Guangzhou 510632,China [4]Center for Bioactive Natural Molecules and Innovative Drugs Research,College of Pharmacy,Jinan University,Guangzhou 510632,China

出　　处：《Acta Pharmaceutica Sinica B》2024年第10期4443-4460,共18页药学学报（英文版）

基　　金：supported by the National Key R&D Program of China(No.2023YFC3503902,China);the National Natural Science Foundation of China(Nos.82293681(82293680);82321004,82204234,and 82273822,China);the Guangdong Basic and Applied Basic Research Foundation(Nos.2022B1515120015 and 2021A1515111021,China);the Guangdong Major Project of Basic and Applied Basic Research(No.2023B0303000026,China);the Guangdong-Hong Kong-Macao Universities Joint Laboratory for the Internationalization of Traditional Chinese Medicine(No.2023LSYS002,China);the Guangzhou Key Laboratory of Traditional Chinese Medicine&Disease Susceptibility(No.2024A03J090,China);the Science and Technology Projects in Guangzhou(No.202102070001,China);supported by the high-performance computing platform of Jinan University.

摘　　要：The building blocks-based molecular network(BBMN)strategy was applied to the phytochemical investigation of Cleistocalyx operculatus,leading to the targeted isolation of eighteen novel cinnamoylphloroglucinol-terpene adducts(CPTAs)with diverse skeleton types(cleistoperones A-R,1-18).Their structures including absolute configurations were determined by extensive spectroscopic methods,quantum chemical calculations,and single-crystal X-ray crystallographic experiments.Cleistoperone A(1),consisting of a cinnamoylphloroglucinol motif and two linear monoterpene moieties,represents an unprecedented macrocyclic CPTA,whose densely functionalized tricyclo[15.3.1.0^(3,8)]heneicosane bridge ring skeleton contains an enolizableβ,β′-triketone system and two different kinds of stereogenic elements(including five point and three planar chiralities).Cleistoperones B and C(2 and 3)are two new skeletal CPTAs with an unusual coupling pattern between the(nor)monoterpene moiety and the cinnamoyl chain of the cinnamoylphloroglucinol unit.Cleistoperone D(4)possesses an unprecedented cage-like 6/6/6/4/6-fused heteropentacyclic scaffold.The plausible biosynthetic pathways for 1-18 were also proposed.Notably,compounds 1,4,7,8,and 18 exhibited significant antiviral activity against respiratory syncytial virus(RSV).The most potent one,cleistoperone A(1)with IC_(50) value of 1.71±0.61μmol/L,could effectively inhibit virus replication via affecting the Akt/mTOR/p70S6K signaling pathway.

关 键 词：Cleistocalyx operculatus Cinnamoylphloroglucinolterpene adduct Targeted isolation Molecular networking Structure elucidation Cleistoperone A Respiratory syncytial virus Antiviral activity 

分 类 号：R914[医药卫生—药物化学]