Prodrug-based nanoassemblies have emerged as advanced carrier-free nanomedicines.These prodrugs typically consist of drug modules,response modules,and modification modules.The general role of modification modules is t...Prodrug-based nanoassemblies have emerged as advanced carrier-free nanomedicines.These prodrugs typically consist of drug modules,response modules,and modification modules.The general role of modification modules is to modulate the self-assembly ability of the prodrugs.How to optimize the structure of modification modules for balanced efficacy and safety of high-toxicity chemotherapeutic drugs deserves to be further investigated.In this study,a modification strategy of aliphatic alcohols with various chain lengths(SC_(4),SC_(8),SC_(12),SC_(16) and SC_(20))was carried out to design five cabazitaxel(CBZ)prodrugs.Among them,CBZ-SC NPs with shorter chain length(SC_(4) and SC_(8))showed poor self-assembly stability.CBZ-SC_(12) NPs also failed to remain stable while the other two CBZ-SC NPs exhibited good stability.In turn,the drug release rate was hindered by the increasing chain length.CBZ-SC12 NPs caused kidney damage due to their high redox-sensitivity and rapid release rate during circulation.By contrast,CBZ-SC NPs with longer chain length(SC_(16) and SC_(20))not only demonstrated superior stability with improved pharmacokinetic behavior,but also might solve the dilemma of dose-related toxicity caused by CBZ.Overall,these findings emphasized the importance of chain length in modification module to modulate the efficacy and safety of CBZ prodrug nanoassemblies.展开更多
Six new aliphatic alcohol and ester compounds of n-octacos-9-enyl propionate （1）, 4-（3-formylheptyl）cyclohexyl 4-（cyclohexylcarbonyloxymethyl）cyclohexyl-carboxylate （2）, n-hentriacont-25-en-5α-ol （3）, n-hex...Six new aliphatic alcohol and ester compounds of n-octacos-9-enyl propionate （1）, 4-（3-formylheptyl）cyclohexyl 4-（cyclohexylcarbonyloxymethyl）cyclohexyl-carboxylate （2）, n-hentriacont-25-en-5α-ol （3）, n-hexetriacont-9,26-dien-8α,11β,23α-triol （4）, n-tetracontan-15α-ol （5） and n-tritetracontan-5α-ol （6） were isolated from the hulls of Oryza sativa. The structures were established on the basis of spectroscopic analysis.展开更多
Straightforward etherification of benzyl alcohols （1） via intermolecular dehydration can be efficiently catalyzed by sodium bisulfite under solvent-free conditions. In the presence of 0.3 mol% or 0.6 mol% amount of ...Straightforward etherification of benzyl alcohols （1） via intermolecular dehydration can be efficiently catalyzed by sodium bisulfite under solvent-free conditions. In the presence of 0.3 mol% or 0.6 mol% amount of sodium bisulfite, symmetric and unsymmetric ethers are prepared from the corresponding alcohols in high yields （up to 95%）. Etherification of benzhydryl alcohols is also discussed.展开更多
Phytopathogenic fungi have attracted great attention as a promising source for new drug discovery.In the progress of our ongoing study for bioactive natural products from an in-house phytopathogenic fungi library,a pa...Phytopathogenic fungi have attracted great attention as a promising source for new drug discovery.In the progress of our ongoing study for bioactive natural products from an in-house phytopathogenic fungi library,a pathogenic fungus,Fusarium proliferatum strain 13294(FP13294),was selected for chemical investigation.Two novel aliphatic unsaturated alcohols named fusariumnols A and B(1 and 2),together with one previously characterized sesquiterpenoid lignoren(3)were identified.Structures of 1-3 were assigned by mass spectrometry and NMR spectroscopy.Their bioactivities were assessed against Staphylococcus epidermidis,S.aureus,and Methicillin-resistant S.aureus(MRSA).Compounds 1 and 2 exhibited weak antibacterial activity against S.epidermidis(MIC=100μM).展开更多
基金support from the Key research and development program of Liaoning Province(No.2024JH2/102500061)Youth innovation team of Liaoning Province Department of Education(No.LJ222410163049)Liaoning Revitalization Talents Program(No.XLYC2203083).
文摘Prodrug-based nanoassemblies have emerged as advanced carrier-free nanomedicines.These prodrugs typically consist of drug modules,response modules,and modification modules.The general role of modification modules is to modulate the self-assembly ability of the prodrugs.How to optimize the structure of modification modules for balanced efficacy and safety of high-toxicity chemotherapeutic drugs deserves to be further investigated.In this study,a modification strategy of aliphatic alcohols with various chain lengths(SC_(4),SC_(8),SC_(12),SC_(16) and SC_(20))was carried out to design five cabazitaxel(CBZ)prodrugs.Among them,CBZ-SC NPs with shorter chain length(SC_(4) and SC_(8))showed poor self-assembly stability.CBZ-SC_(12) NPs also failed to remain stable while the other two CBZ-SC NPs exhibited good stability.In turn,the drug release rate was hindered by the increasing chain length.CBZ-SC12 NPs caused kidney damage due to their high redox-sensitivity and rapid release rate during circulation.By contrast,CBZ-SC NPs with longer chain length(SC_(16) and SC_(20))not only demonstrated superior stability with improved pharmacokinetic behavior,but also might solve the dilemma of dose-related toxicity caused by CBZ.Overall,these findings emphasized the importance of chain length in modification module to modulate the efficacy and safety of CBZ prodrug nanoassemblies.
文摘Six new aliphatic alcohol and ester compounds of n-octacos-9-enyl propionate （1）, 4-（3-formylheptyl）cyclohexyl 4-（cyclohexylcarbonyloxymethyl）cyclohexyl-carboxylate （2）, n-hentriacont-25-en-5α-ol （3）, n-hexetriacont-9,26-dien-8α,11β,23α-triol （4）, n-tetracontan-15α-ol （5） and n-tritetracontan-5α-ol （6） were isolated from the hulls of Oryza sativa. The structures were established on the basis of spectroscopic analysis.
文摘Straightforward etherification of benzyl alcohols （1） via intermolecular dehydration can be efficiently catalyzed by sodium bisulfite under solvent-free conditions. In the presence of 0.3 mol% or 0.6 mol% amount of sodium bisulfite, symmetric and unsymmetric ethers are prepared from the corresponding alcohols in high yields （up to 95%）. Etherification of benzhydryl alcohols is also discussed.
基金This work was supported by the National Key Research and Development Program of China(2020YFA0907200,2019YFA0906200,and 2020YFA0907800)the National Natural Science Foundation of China(21877038,21907031,21977029,31720103901,and 81903529)+1 种基金Shanghai Rising-Star Program(20QA1402800)the Open Project Funding of the State Key Laboratory of Bioreactor Engineering,and the 111 Project(B18022).
文摘Phytopathogenic fungi have attracted great attention as a promising source for new drug discovery.In the progress of our ongoing study for bioactive natural products from an in-house phytopathogenic fungi library,a pathogenic fungus,Fusarium proliferatum strain 13294(FP13294),was selected for chemical investigation.Two novel aliphatic unsaturated alcohols named fusariumnols A and B(1 and 2),together with one previously characterized sesquiterpenoid lignoren(3)were identified.Structures of 1-3 were assigned by mass spectrometry and NMR spectroscopy.Their bioactivities were assessed against Staphylococcus epidermidis,S.aureus,and Methicillin-resistant S.aureus(MRSA).Compounds 1 and 2 exhibited weak antibacterial activity against S.epidermidis(MIC=100μM).
