ABSTRACT
It is demonstrated that natural product vindoline can enhance the glucose-stimulated insulin secretion (GSIS) in MIN6 cells with the EC50 value of 50.2µM. In order to improve the activities, a series of vindoline derivatives are synthesized and evaluated in MIN6 cells. Compounds 4, 8, 17 and 24 show about 4.5 times more effective stimulation insulin secretion ability (EC50: 10.4, 14.2, 11.0 and 12.7µM, respectively) than vindoline.
Subject(s)
Glucose , Insulin-Secreting Cells/drug effects , Insulin/metabolism , Vinblastine/analogs & derivatives , Animals , Cell Line , Hypoglycemic Agents/chemical synthesis , Hypoglycemic Agents/pharmacology , Inhibitory Concentration 50 , Insulin Secretion , Mice , Molecular Structure , Vinblastine/chemical synthesis , Vinblastine/chemistry , Vinblastine/pharmacologyABSTRACT
The natural product arctigenin (ATG) demonstrated preferential cytotoxicity to cancer cells under glucose starvation. A series of 4-amino-4-dehydroxylarctigenin derivatives based on lead compound ATG were designed and synthesized by bioisosteric modifications. Their cytotoxicities were evaluated in glucose-starved A549 tumor cells and the results indicated that the 4-amino-4-dehydroxylarctigenin showed more potent cytotoxicity than arctigenin, and the further substituent group on 4-amino would result in the cytotoxicities decreased significantly. 4-Substituted-arctigenin could selectively target on glucose-starved A549 tumor cells which provide an alternative strategy for anticancer drug development with minimal normal tissue toxicity.
Subject(s)
4-Butyrolactone/analogs & derivatives , Antineoplastic Agents, Phytogenic/chemical synthesis , Furans/chemistry , Lignans/chemical synthesis , 4-Butyrolactone/chemical synthesis , 4-Butyrolactone/chemistry , 4-Butyrolactone/toxicity , Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/toxicity , Apoptosis/drug effects , Cell Line, Tumor , Furans/toxicity , Glucose/pharmacology , Humans , Lignans/chemistry , Lignans/toxicity , Structure-Activity RelationshipABSTRACT
Extracts of Toona sinensis shoots were studied to identify the precursors of volatile sulfur-containing flavor molecules. T. sinensis was found to contain new compounds (S,S)-γ-glutamyl-(cis-S-1-propenyl)thioglycine, 1, (S,S)-γ-glutamyl-(trans-S-1-propenyl)thioglycine, 2, and γ-glutamyl-(cis-S-1-propenyl)-cysteine, 3. The structures of these compounds were determined by interpretation of multistage mass spectrometric (MS(n)), 1D, and 2D NMR data. The absolute configuration of 1 was established by comparison of experimental with computed infrared and vibrational circular dichroism spectra. Because of the flexibility of the molecule and the novelty of the structure, the configuration was further confirmed by X-ray crystallography. Compounds 1 and 2 are the first examples of norcysteine-containing metabolites reported from nature. They may release thiols via cleavage of the amide bond by proteases, followed by spontaneous decomposition of the resulting unstable alk(en)yl norcysteine moiety.
Subject(s)
Cysteine/analogs & derivatives , Meliaceae/chemistry , Plant Extracts/chemistry , Vegetables/chemistry , Circular Dichroism , Crystallography, X-Ray , Cysteine/metabolism , Magnetic Resonance Spectroscopy , Meliaceae/metabolism , Molecular Structure , Plant Extracts/metabolism , Vegetables/metabolismABSTRACT
Jatrophalactam (1), a novel diterpenoid lactam possessing an unprecedented 5/13/3 tricyclic skeleton, was isolated from the roots of Jatropha curcas. The structure and relative configuration of jatrophalactam (1) were elucidated by extensive spectroscopic analysis and further determined by a single-crystal X-ray diffraction.
Subject(s)
Diterpenes/isolation & purification , Jatropha/chemistry , Lactams/isolation & purification , Crystallography, X-Ray , Diterpenes/chemistry , Diterpenes/pharmacology , Drug Screening Assays, Antitumor , Humans , Lactams/chemistry , Lactams/pharmacology , Molecular Conformation , Molecular Structure , Nuclear Magnetic Resonance, Biomolecular , Plant Roots/chemistryABSTRACT
Six new terpenoids, including three diterpenoids (1-3), one norditerpenoid (4) and two sesquiterpenoids (11 and 12), were isolated from the roots of Chloranthus henryi. The structures were elucidated mainly by 1D, and 2D NMR and MS experiments, and their relative configurations were determined by NOE techniques.
Subject(s)
Plants/chemistry , Terpenes/chemistry , Mass Spectrometry , Nuclear Magnetic Resonance, Biomolecular , Plant Roots/chemistry , Terpenes/isolation & purificationABSTRACT
Two sequential Suzuki coupling reactions have been developed for efficient synthesis of synthetically and biologically important 3,6-disubstituted 2,5-dioxybenzoquinone architectures in a highly chemoselective controlled manner. The method serves as a key step in the total synthesis of leucomelone in three steps and in 61% overall yield.
Subject(s)
Benzoquinones/chemical synthesis , Boronic Acids/chemistry , Catechols/chemical synthesis , Benzoquinones/chemistry , Catalysis , Catechols/chemistry , Combinatorial Chemistry Techniques , Molecular StructureABSTRACT
A new Daphniphyllum alkaloid daphnicyclidin L (1), containing a rare cyclopentadienyl anion, which is stabilized as a zwitterion by an internal iminium counterion, was isolated from the stem barks of Daphniphyllum macropodum Miq., together with four known alkaloids: daphnicyclidin D (2), daphnicyclidin H (3), deoxyyuzurimine (4), and yuzurimine (5). The structures were elucidated on the basis of spectroscopic data. The configuration of 1 was elucidated by single-crystal X-ray diffraction crystallography.
