Structure modification,antialgal,antiplasmodial,and toxic evaluations of a series of new marine-derived 14-membered resorcylic acid lactone derivatives  

作　　者：Wei-Feng Xu Na-Na Wu Yan-Wei Wu Yue-Xuan Qi Mei-Yan Wei Laura M.Pineda Michelle G.Ng Carmenza Spadafora Ji-Yong Zheng Ling Lu Chang-Yun Wang Yu-Cheng Gu Chang-Lun Shao 

机构地区：[1]Key Laboratory of Marine Drugs,the Ministry of Education of China,School of Medicine and Pharmacy,Ocean University of China,Qingdao,266003,China [2]Laboratory for Marine Drugs and Bioproducts,Qingdao National Laboratory for Marine Science and Technology,Qingdao,266237,China [3]State Key Laboratory for Marine Corrosion and Protection,Luoyang Ship Material Research Institute(LSMRI),Qingdao,266237,China [4]Center of Cellular and Molecular Biology of Diseases,Instituto de Investigaciones Científcas y Servicios de Alta Tecnología,City of Knowledge,Clayton,Apartado,0816-02852,Panama [5]Syngenta Jealott’s Hill International Research Centre,Bracknell,Berkshire,RG426EY,UK

出　　处：《Marine Life Science & Technology》2022年第1期88-97,共10页海洋生命科学与技术（英文）

基　　金：supported by the Program of National Natural Science Foundation of China(Nos.U1706210,41776141,42006092,41322037 and 41830535);the Fundamental Research Funds for the Central Universities(No.201841004);the Marine S&T Fund of Shandong Province for Pilot National Laboratory for Marine Science and Technology(Qingdao)(No.2018SDKJ0403-2);the Research Fund of State Key Laboratory for Marine Corrosion and Protection of Luoyang Ship Material Research Institute(LSMRI)[No.KF190402],and the Taishan Scholars Program,China(No.tsqn20161010);funded by a SENACYT grant(FID17-095)and partially by the National System of Investigators(SNI)of Panama.

摘　　要：Marine natural products play critical roles in the chemical defense of many marine organisms and are essential,reputable sources of successful drug leads.Sixty-seven 14-membered resorcylic acid lactone derivatives 3–27 and 30–71 of the natural product zeaenol(1)isolated from the marine-derived fungus Cochliobolus lunatus were semisynthesized by chlorination,acylation,esterification,and acetalization in one to three steps.The structures of these new derivatives were established by HRESIMS and NMR techniques.All the compounds(1–71)were evaluated for their antialgal and antiplasmodial activities.Among them,14 compounds displayed antifouling activities against adhesion of the fouling diatoms.In particular,9 and 34 exhibited strong and selective inhibitory effects against the diatoms Navicula laevissima and Navicula exigua(EC50=6.67 and 8.55μmol/L),respectively,which were similar in efficacy to those of the positive control SeaNine 211(EC50=2.90 and 9.74μmol/L).More importantly,38,39,and 69–71 showed potent antiplasmodial activities against Plasmodium falciparum with IC50 values ranging from 3.54 to 9.72μmol/L.Very interestingly,the five antiplasmodial derivatives displayed non-toxicity in the cytotoxicity assays and the zebrafish embryos model,thus,representing potential promising antiplasmodial drug agents.The preliminary structure–activity relationships indicated that biphenyl substituent at C-2,acetonide at positions C-5′and C-6′,and tri-or tetra-substituted of acyl groups increased the antiplasmodial activity.Therefore,combining evaluation of chemical ecology with pharmacological models will be implemented as a systematic strategy,not only for environmentally friendly antifoulants but also for structurally novel drugs.

关 键 词：Marine natural product 14-Membered resorcylic acid lactone Zeaenol SEMISYNTHESIS Antialgal activity Antiplasmodial activity 

分 类 号：P745[天文地球—海洋生物学]