Chemical epigenetic manipulation was applied to the zoanthid-derived fungus Cochliobolus lunatus(TA26-46)with a histone deacetylation modifier(100μmol L^(−1) nicotinamide),resulting in the isolation of a new 14-membe...Chemical epigenetic manipulation was applied to the zoanthid-derived fungus Cochliobolus lunatus(TA26-46)with a histone deacetylation modifier(100μmol L^(−1) nicotinamide),resulting in the isolation of a new 14-membered resorcylic acid lactone named 7′(Z)-zeaenol(1),together with six known analogues(2−7)from the treated broth.The planar structure of 1 was determined by comprehensive NMR spectroscopy and HRESIMS data.The absolute configuration of 1 was elucidated by ECD spectrum,^(13)C NMR shift calculations,and on the basis of biogenetic considerations.Compound 5 exhibited cytotoxic activity against the human tumor cell lines A549,HCT-116,HT-29,Hela,MCF-7,and K562 with the IC_(50) values ranging from 2.54 to 7.44μmolL^(−1).展开更多
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–...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.展开更多
The construction of the C(1) - C(5) fragment of the resorcylic acid lactone pochonin J is described. The synthesis is marked by the installation of the cis-1,3-diol moiety in a highly stereoselective manner using Evan...The construction of the C(1) - C(5) fragment of the resorcylic acid lactone pochonin J is described. The synthesis is marked by the installation of the cis-1,3-diol moiety in a highly stereoselective manner using Evans’ intra-molecular base-catalyzed oxyconjugate addition of a hemiacetal-derived nucleophile. The synthetic route presented affords an efficient pathway to the preparation of this critical architectural feature that should facilitate the development of this secondary metabolite as a potential drug candidate.展开更多
基金supported by the National Natural Science Foundation of China(Nos.81673350,81703411,41776156)the National Science and Technology Major Project for Significant New Drugs Development,China(No.2018ZX09735-004)+1 种基金the Fundamental Research Funds for the Central Universities of China(No.201962002)the Taishan Scholars Program,China.
文摘Chemical epigenetic manipulation was applied to the zoanthid-derived fungus Cochliobolus lunatus(TA26-46)with a histone deacetylation modifier(100μmol L^(−1) nicotinamide),resulting in the isolation of a new 14-membered resorcylic acid lactone named 7′(Z)-zeaenol(1),together with six known analogues(2−7)from the treated broth.The planar structure of 1 was determined by comprehensive NMR spectroscopy and HRESIMS data.The absolute configuration of 1 was elucidated by ECD spectrum,^(13)C NMR shift calculations,and on the basis of biogenetic considerations.Compound 5 exhibited cytotoxic activity against the human tumor cell lines A549,HCT-116,HT-29,Hela,MCF-7,and K562 with the IC_(50) values ranging from 2.54 to 7.44μmolL^(−1).
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)+2 种基金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.
文摘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.
文摘The construction of the C(1) - C(5) fragment of the resorcylic acid lactone pochonin J is described. The synthesis is marked by the installation of the cis-1,3-diol moiety in a highly stereoselective manner using Evans’ intra-molecular base-catalyzed oxyconjugate addition of a hemiacetal-derived nucleophile. The synthetic route presented affords an efficient pathway to the preparation of this critical architectural feature that should facilitate the development of this secondary metabolite as a potential drug candidate.