Ethyl 3,9-dihydroxy-9-methyl-7-phenyl-7,8,10-trihydro-6H-dibenzo[b,d]pyran-6-one-8-carboxylate(C(23)H(22)O6,Mr = 394.42) has been synthesized and its structure was determined by ~1H and ^(13)C NMR,ESI-MS,eleme...Ethyl 3,9-dihydroxy-9-methyl-7-phenyl-7,8,10-trihydro-6H-dibenzo[b,d]pyran-6-one-8-carboxylate(C(23)H(22)O6,Mr = 394.42) has been synthesized and its structure was determined by ~1H and ^(13)C NMR,ESI-MS,elemental analysis,and X-ray single-crystal diffraction.The crystal belongs to the triclinic system,space group P1,with a = 8.8220(17),b = 9.881(2),c = 12.157(2) A,α= 90.488(3),β= 102.664(4),γ= 98.799(3)°,V= 1020.8(3) A^3,Z= 2,Dc = 1.342 g/cm^3,μ= 0.099mm^(-1),F(000) = 436,R = 0.0615 and wR = 0.2501 for 2592 observed reflections with(I2σ(I)).In the crystal structure,the coumarin ring system is planar and the 3:4 fused cyclohexane ring adopts distorted half-chair conformation.Rich hydrogen bonding interactions are formed between compound 2 and lattice water molecules.These interactions assemble molecules of 2 into 2D layered networks in an AB stacking sequence.Its in vitro antiproliferative activities against three human cancer cell lines were evaluated by MTT assay.展开更多
The novel crystal of the title compound 2-(((5-(((5,7-dimethyl-[1,2,4]triazolo-[1, 5-a]-pyrimidin-2-yl)thio)methyl)-4-phenyl-4H-1,2,4-triazol-3-yl)thio)methyl)-4H-chromen-4-one methanol solvate(C27H25N7O3...The novel crystal of the title compound 2-(((5-(((5,7-dimethyl-[1,2,4]triazolo-[1, 5-a]-pyrimidin-2-yl)thio)methyl)-4-phenyl-4H-1,2,4-triazol-3-yl)thio)methyl)-4H-chromen-4-one methanol solvate(C27H25N7O3S2, Mr = 559.66) has been prepared and its structure was determined by single-crystal X-ray diffraction. The crystal belongs to the monocline system, space group P21/c with a = 11.9879(9), b = 14.0743(10), c = 15.9706(11)A, β = 98.509(2)°, V = 2664.9(3)A3, Z = 4, Dc = 1.395 g/cm^3, F(000) = 1168, μ = 0.116 mm-1, MoKa radiation(λ = 0.71073), R = 0.0652, and wR = 0.1425 for 5220 observed reflections with I 〉 2σ(I). X-ray diffraction analyses reveal that the molecule adopts a C-shape. The planes of the benzopyrone and triazolopyrimidine were nearly parallel to each other, with a dihedral angle of 1.21(3)°. Intramolecular and intermolecular hydrogen bonds together with π-π interations are found to exist in the structure. The results of MTT assay indicate that the title compound displays excellent antiproliferative activity against two human cancer cell lines.展开更多
The crystal structure of the new title compound 2,2-dimethyl-4-oxochroman-3-ylmorpholine-4-carbodithioate(C16H19NO3S2,Mr = 337.44) has been prepared and determined by single-crystal X-ray diffraction.The crystal is ...The crystal structure of the new title compound 2,2-dimethyl-4-oxochroman-3-ylmorpholine-4-carbodithioate(C16H19NO3S2,Mr = 337.44) has been prepared and determined by single-crystal X-ray diffraction.The crystal is of triclinic,space group P1 with a = 9.5518(7),b = 9.7172(7),c = 11.0220(8),α = 67.08(1),β = 74.66(1),= 61.31(1)°,V = 822.72(10)3,Z = 2,Dc = 1.362 g/cm3,F(000) = 356,μ = 0.092 mm-1,MoKa radiation(λ = 0.71073),R = 0.0515 and wR = 0.1389 for 2623 observed reflections with I 2(I).X-ray diffraction analysis reveals that the chroman ring adopts a half-chair conformation while the morpholine ring shows a chair conformation.Intramolecular and intermolecular C–H···S and C–H···O hydrogen bonds together with π-π interations are found in the structure.The result of MTT assay shows the title compound displays good antiproliferative activity against two human cancer cell lines.展开更多
In our efforts to identify novel potent anticancer agents, we synthesized a series of 2,7-disubstituted triazolo[1,5-a]pyrimidines (6-16). Their antiproliferative activity against Bel-7402, HT- 1080 and WI-38 cell l...In our efforts to identify novel potent anticancer agents, we synthesized a series of 2,7-disubstituted triazolo[1,5-a]pyrimidines (6-16). Their antiproliferative activity against Bel-7402, HT- 1080 and WI-38 cell lines was tested by MTT assay in vitro. Four of the compounds (9-11 and 16) displayed promising antiproliferative activity superior to gefitinib, especially compound 9. A preliminary SAR study of these derivatives was performed.展开更多
A series of novel N-anilino-2-substituted-5-methyl-[1,2,4]triazolo[1,5-a]pyrimidine-7-amine derivatives was prepared and evaluated for their in vitro antiproliferative activity against two cancer cell lines,Bel-7402 a...A series of novel N-anilino-2-substituted-5-methyl-[1,2,4]triazolo[1,5-a]pyrimidine-7-amine derivatives was prepared and evaluated for their in vitro antiproliferative activity against two cancer cell lines,Bel-7402 and HT-1080.Most of the compounds inhibited the cell proliferation at a low concentration.Seven compounds,VI5,VI7,VI10,and VI12―VI15,possessed marked antiproliferative activity superior to that of cisplatin.Of these seven initial hits,compound VI10 was the most active.展开更多
Many small-molecule compounds have been evaluated with potential antiproliferative activities. Ethyl 1-(phenylcarbamoyl)-2-(3,4,5-trimethoxyphenyl)cyclopropanecarboxylate, one novel cyclopropylamide analogue of co...Many small-molecule compounds have been evaluated with potential antiproliferative activities. Ethyl 1-(phenylcarbamoyl)-2-(3,4,5-trimethoxyphenyl)cyclopropanecarboxylate, one novel cyclopropylamide analogue of combretastatin-A4(CA-4), has been synthesized and its crystal structure was characterized by X-ray single-crystal diffraction. The crystal belongs to monoclinic, space group P21/n, with a = 15.0263(3), b = 7.6574(2), c = 19.4117(4), β = 111.9010(10)o, V = 2072.36(8)3, Z = 4, C22H24NO6, Mr = 398.42, Dc = 1.277 Mg/cm3, F(000) = 844, λ(MoKα) = 1.54178 , μ = 0.770 mm–1, R = 0.0546 and wR = 0.1889 for 3319 observed reflections(I 〉 2σ(I)). Meanwhile, the compound revealed potential antiproliferative activities in several cancer cells in vitro.展开更多
Cajanine,a constituent of Cajanaus cajan L.,used in traditional Chinese medicine,is a promising drug candidate because of its broad range of bioactivities.However,the total synthesis of cajanine and its derivatives ha...Cajanine,a constituent of Cajanaus cajan L.,used in traditional Chinese medicine,is a promising drug candidate because of its broad range of bioactivities.However,the total synthesis of cajanine and its derivatives has never been reported.Herein,we report the total synthesis of cajanine in nine steps with an overall yield of 10%together with its analog,longistyline A,in 8%yield.The antiproliferative activity of the two compounds against a human hepatoma cell line is also reported.展开更多
A series of novel 4-substituted-phenoxy-benzamide derivatives bearing an aryl cycloaliphatic amine moiety were synthesized and evaluated for antiproliferative activity against SW620, HT29 and MGC803 cancer cell lines ...A series of novel 4-substituted-phenoxy-benzamide derivatives bearing an aryl cycloaliphatic amine moiety were synthesized and evaluated for antiproliferative activity against SW620, HT29 and MGC803 cancer cell lines in vitro. The pharmacological data demonstrated that the majority of target compounds exhibited moderate efficacy in HT29 and MGC803 cell lines. Compound 10 c showed promising inhibition of hedgehog(Hh) signaling pathway in an Hh-related assay. In addition, the superposition pattern of 10 c showed a good fit for a pharmacophoric model generated by Hh inhibitors and provided a basis for further structural optimization.展开更多
Three novel norcantharidin acylamide acids (L1 =N-thiadiazole norcantharidin acylamide acid, CIoHIlN304S; L2=N-thiazole norcantharidin acylamide acid, CjIHI2N204S and L3=N-benzothiazole norcantharidin acylamide acid,...Three novel norcantharidin acylamide acids (L1 =N-thiadiazole norcantharidin acylamide acid, CIoHIlN304S; L2=N-thiazole norcantharidin acylamide acid, CjIHI2N204S and L3=N-benzothiazole norcantharidin acylamide acid, C15H14N204S) were synthesized by the reactions of norcantharidin (NCTD=7-oxabicyclo[2,2,1 ]heptane-2,3- dicarboxylic acid anhydride, C8H8O4) with 2-amino-1,3,4-thiadiazole (C2H3N3S), 2-aminothiazole (C3H4N2S) and 2-aminobenzothiazole (C7H6N2S), respectively. Their structures were characterized by elemental analysis, IR, and NMR. The inhibition rates of L3 was much higher than those of Lj and L2 against human hepatoma cells SMMC7721 cell lines in vitro. The interaction between the compounds and DNA was studied by means of fluorescence quenching studies and viscosity measurements. The emission intensities decreased obviously with increasing concentration of the compounds in the fluorescence quenching experiments. The linear Stern-Volmer quenching constant Ksq values were 0.62 (Ll), 0.55 (L2) and 1.08 (L3), respectively. The binding abilities followed the trend from high to low were L3, L1 and L2, respectively. The results of viscosity measurements showed that L1 and L2 might bind to DNA via partial intercalation, while L3 bound mainly in intercalation.展开更多
With chenodeoxycholic acid as starting material,a series of lactam derivatives of chenodeoxycholic acid was synthesized and their antiproliferative activities against some cancer cells were determined.Among the synthe...With chenodeoxycholic acid as starting material,a series of lactam derivatives of chenodeoxycholic acid was synthesized and their antiproliferative activities against some cancer cells were determined.Among the synthesized derivatives,compounds 6 and 18 displayed distinct antiproliferative activity against PC-3,H-292,SKBR3 and Hey-1B cancer cells,and compounds 10,17 and 18 showed significant antiproliferative activity against SKBR3 cells.Our results reveal that the position of hydroximino on ring A or B of the parental scaffold dramatically affects the antiproliferative activity of these compounds.The conversion of 7-hydroximino to other substituent or 7-hydroximino to 3-hydroximino in the compounds resulted in a dramatic decrease of the antiproliferative activity,suggesting the importance of 7-hydroximino group for the biological activity of the compounds.The structure/activity correlation generated from the studies provides valuable information for the further design of novel chemotherapeutic drugs.展开更多
In the last years, sugar beet pectins have been the subject of several investigations involving extraction methodologies, chemical composition and functional properties. The structure of pectins, which depends on the ...In the last years, sugar beet pectins have been the subject of several investigations involving extraction methodologies, chemical composition and functional properties. The structure of pectins, which depends on the extraction method, is decisive in their capacity to induce apoptosis on several cancer cell lines like colon, prostate and breast. In this work, sugar beet pectin extraction was performed in the following steps: lipid extraction with hexane, removal of soluble complex carbohydrates and proteins, and enzymatic treatment with amyloglucosidase, protease, and pectinase. The enzymatic treatment was carried out with Rohapect DA6L under the following conditions: 50℃, pH 4.0, 2% enzyme/substrate (E/S) ratio, 15 h, and a solid to liquid ratio of 1 : 10. The pectic extract showed a degree of polymerization (DP) profile of 55.8% with DP≥7; 4.9% with DP6; 5.8% between DP2 and DP6 ; 4.7% with DP2; and 28.8% with DP1. The pectic extract was examined for its antiproliferative activity on the MCF-7 breast cancer cell line. At a concentration range of 12.5-25 mg/mL the pectic extract killed 80.6% of the cells, exhibiting a higher antiproliferative activity than 4-hydroxytamoxifen (4- OHT), a classical anticancer drug, which killed 56.5% of the cells.展开更多
A novel crystal with the molecular formula [Pd(DCA)(bipy)]2 [Pd(bipy)Cl2 ]·6.75H2O was formed by PdCl2 with disodium demethylcantharate (Na2 (DCA),DCA2= 7-oxa-bicyclo[2.2.1]heptane-2,3-bicarboxylate) an...A novel crystal with the molecular formula [Pd(DCA)(bipy)]2 [Pd(bipy)Cl2 ]·6.75H2O was formed by PdCl2 with disodium demethylcantharate (Na2 (DCA),DCA2= 7-oxa-bicyclo[2.2.1]heptane-2,3-bicarboxylate) and 2,2-bipyidine (bipy) through the hydrothermal method.The complex was characterized by elemental analysis and infrared spectroscopy.The structure of the complex was determined by single-crystal X-ray diffraction,which is of triclinic system,space group P1 with a=13.6818(7),b=14.8426(8),c=15.0043(8),α=97.319(3),β=92.521(3),γ=105.776(2)°,V=2898.4(3) 3,Dc=1.545 g·cm-3,Z=1,F(000)=1420,S=0.852,the final R=0.0525 and wR=0.1777 for 13634 observer reflections (I〉2σ(I)).The binding reaction of the complex with ct-DNA and bovine serum albumin (BSA) was studied by fluorescence spectroscopy.The results indicated that the complex binds to ct-DNA via the partial intercalation.The binding constant K A of the complex interaction with BSA was 3.98×10 5 L·mol-1 and one binding site would be formed.The antiproliferative activity of the complex against human hepatoma cells (SMMC7721) in vitro is much higher than that of Na 2 (DCA).展开更多
Bioassay-guided fractionation of EtOH extracts obtained from the roots and wood of the Madagascan plant Leptaulus citroides Baill.(Cardiopteridaceae)led to the isolation of ethyl esters of three new triterpenoid sapon...Bioassay-guided fractionation of EtOH extracts obtained from the roots and wood of the Madagascan plant Leptaulus citroides Baill.(Cardiopteridaceae)led to the isolation of ethyl esters of three new triterpenoid saponins(1–3)and the known sesquiterpenoid cinnamosmolide(4).The structures of 1–3 were elucidated by extensive 1D and 2D NMR experiments and mass spectrometry.Compounds 1,2,and 4 showed moderate cytotoxicity against the A2780 human ovarian cancer cell line with IC50 values of 2.8,10.2 and 2.0 lM,respectively.展开更多
A novel series of 5H-pyridazino[4,5-b]indoles were designed and synthesized in order to find novel potent anticancer compounds. The structures were confirmed by ^1H NMR and MS. Their antiproliferative activities again...A novel series of 5H-pyridazino[4,5-b]indoles were designed and synthesized in order to find novel potent anticancer compounds. The structures were confirmed by ^1H NMR and MS. Their antiproliferative activities against two cancer cell lines were tested by the MTT method in vitro. Three of compounds (1e, 1g, and 1h) exhibited potent antiproliferative activities, especially compound lh (with IC50 values of 5.2 μmol/L and 1.9 μmol/L against Bel-7402 and HT-1080, respectively). The preliminary structure-activity relationships of 5H-pyridazino[4,5-b]indole derivatives were discussed.展开更多
Rumex nepalensis Spreng.(Polygonaceae) commonly known as Nepal Dock has wide-spectrum therapeutic potencies and is extensively used for centuries in traditional medicine systems. The leaves of this plant are edible an...Rumex nepalensis Spreng.(Polygonaceae) commonly known as Nepal Dock has wide-spectrum therapeutic potencies and is extensively used for centuries in traditional medicine systems. The leaves of this plant are edible and a rich source of natural antioxidants. They act as a possible food supplement and are largely used in pharmaceutical industry. Extracts and metabolites from this plant exhibits pharmacological activities including anti-inflammatory, antioxidant, antibacterial, antifungal, antiviral, insecticidal, purgative, analgesic, antipyretic, anti-algal, central nervous system depressant, genotoxic, wound healing and skeletal muscle relaxant activity. Due to its remarkable biological activities, it has the potential to act as a rich source of drug against life threatening diseases. However, more studies are needed to scientifically validate the traditional uses of this plant, beside isolating and identifying their active principles and characterizing the mechanisms of action. We present herein a critical account of its botany, ecology, traditional uses, phytoconstituent profile and major pharmacological activities reported in recent years and therefore will provide a source of information on this plant for further studies.展开更多
Osmundea pinnatifida is a red edible seaweed known as pepper dulse.O.pinnatifida was cultivated in the farm of ALGAplus(ílhavo,Portugal).This farm is integrated with a seabream and seabass commercial aquaculture ...Osmundea pinnatifida is a red edible seaweed known as pepper dulse.O.pinnatifida was cultivated in the farm of ALGAplus(ílhavo,Portugal).This farm is integrated with a seabream and seabass commercial aquaculture and uses the nutrient-enriched water resultant from the fish production as its cultivation medium in the integrated multi-trophic aquaculture(IMTA)manner.Wild and IMTA-cultivated samples of O.pinnatifi da were screened for antioxidant and antitumor activities.The antioxidant capacity of solvent extracts from wild and IMTA cultivated samples was assessed in two methods(2,2-diphenyl-1-picrylhydrazyl(DPPH)and oxygen radical absorbance capacity(ORAC)),and their total phenolic contents(TPC)were estimated.Antitumor activity was evaluated in three different tumor cell lines(HepG-2,MCF-7,and SH-SY5Y)through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT)assay.Among the solvents used for extraction,dichloromethane was the most eff ective to extract phenolic compounds and presented higher ORAC.A significant correlation was found between TPC and ORAC,which was also sustained by the principal components analysis(PCA).Dichloromethane extracts induced a cytostatic eff ect on MCF-7 cells and showed weak cytotoxicity to SH-SY5Y cells and weak impact on cell proliferation.Overall,there were no statistically signifi cant differences in the biological activities shown by the wild and IMTA-cultivated samples.Hence,O.pinnatifida can be obtained in an economical and environmentally sustainable way through IMTA,maintaining bioactive properties in a high potential for further nutraceutical purposes.展开更多
Histone deacetylases(HDACs) are considered to be among the most promising targets for the development of anti-cancer drugs,and HDAC inhibitors(HDACIs) have become a promising class of anti-cancer drugs.To explore ...Histone deacetylases(HDACs) are considered to be among the most promising targets for the development of anti-cancer drugs,and HDAC inhibitors(HDACIs) have become a promising class of anti-cancer drugs.To explore whether thioacetyl group as the zinc binding group(ZBG) and a slight change in the hydrophobicity of the recognition domain of HDACIs could alter their activities,we synthesized a series of cyclo[-L-Am7(SAc)-Aib-L-Phe(n-Cl)D-Pro-] and evaluated their HDAC-inhibitory and antiproliferative activities.The results show that these peptides could inhibit HDAC at 10-9 mol/L level,and could selectively inhibit the proliferation of three human cancer cell lines with IC 50 at 10-6 mol/L level.Docking study was conducted to examine the mechanisms by which these peptides interact with HDAC2.It appeared that a zinc ion in the active site of HDAC was coordinated by the carbonyl oxygen atom of the ZBG in the inhibitor.Both the ZBG domain of all the peptides and the surface recognition domain of cyclo[-L-Am7(SAc)-Aib-L-Phe(o-Cl)-D-Pro-] and that of cyclo[-L-Am7(SAc)-Aib-L-Phe(m-Cl)-D-Pro-] interacted with HDAC2 via hydrogen bonding.Hydrophobic interaction has been considered to provide favorable contributions to stabilizing the complexes,and the introduction of a chlorine atom at the aromatic ring on the L-Phe position of these peptides affected the interaction between each of these inhibitors and the enzyme,resulting in slight change in the structure of the surface recognition domain of the peptides.展开更多
Twenty prenylated flavonoids 1-20 were synthesized by glycoside hydrolysis, dehydrogenation, selective O-methylation, O-prenylation and Claisen rearrangement reaction, from abundant and inexpensive natural flavonoids ...Twenty prenylated flavonoids 1-20 were synthesized by glycoside hydrolysis, dehydrogenation, selective O-methylation, O-prenylation and Claisen rearrangement reaction, from abundant and inexpensive natural flavonoids naringin, hespiredin, quercetin and myricetin. Among them, 1-7, 10-15 and 17-20 are novel compounds, the natural product 3,3',4',7-tetramethoxy-8-prenyl-5-hydroxy flavonoid(16) was synthesized in a high yield. Their antiprolirative activities were evaluated in vitro on a panel of three human cancer cell lines(HeLa, HCC1954 and SK-OV-3). The results show that most of the target compounds displayed moderate to potent antiprolirative activities against the three cancer cells with half maximal inhibitory concentration(ICs0) values from 0.49 μmol/L to 95.07 μmol/L. Among them, 3′,4′,7-trimethoxyl-5-hydroxyl-8-prenyl flavonoid(12) exhibited the strongest antiprolirative activity against the three cancer cells mentioned above with IC50 values of 0.91-7.08 μmol/L. 3′,7-Dimethoxy-5-O- prenyl flavone(6) and 3′,4′,7-trimethoxy-5-O-prenyl flavone(10) showed selective antiproliferative activity against HCC1954 cells with TC50 value of 0 49 and 5 .32μmol/L, respectively.展开更多
Four new cyclohexapeptides,pyridapeptides F–I(1–4),were isolated from the fermentation broth of marine sponge-derived Streptomyces sp.OUCMDZ-4539.The pyridapeptides F–H(1–3)are composed ofβ-hydroxyleucine,alanine...Four new cyclohexapeptides,pyridapeptides F–I(1–4),were isolated from the fermentation broth of marine sponge-derived Streptomyces sp.OUCMDZ-4539.The pyridapeptides F–H(1–3)are composed ofβ-hydroxyleucine,alanine,O-methylthreonine,hexahydropyridazine-3-carboxylic acid,5-hydroxytetrahydropyridazine-3-carboxylic acid,and(2S,3R,4E,6E)-2-amino-3–hydroxy-4,6-dienoic acid residues.Pyridapeptide I(4)contains(2S,3R,4E,6E)-2-amino-3–hydroxy-8-methylnona-4,6-dienoic acid residue and a very rare glycose residue,aculose.Their structures were determined based on spectroscopic analysis and chemical methods.Pyridapeptides G–I(2–4)have the 2,3,6-trideoxyhexose units glycosylated at theγ-OH-TPDA residue,displayed significant antiproliferative activity against four(PC9,MKN45,Hep G2,K562)or two(PC9,MKN45)human cancer cell lines.展开更多
Objective:To study constituents of the leaves of Macaranga hemsleyana,and evaluate their inhibitory effects against NOD-like receptor thermal protein domain associated protein 3(NLRP3)inflammasome activation,and antip...Objective:To study constituents of the leaves of Macaranga hemsleyana,and evaluate their inhibitory effects against NOD-like receptor thermal protein domain associated protein 3(NLRP3)inflammasome activation,and antiproliferative activity.Methods:The constituents were isolated and purified by column chromatography on MCI gel CHP20P/P120,silica gel,Sephadex LH-20,and HPLC.The structures of compounds were determined by 1D,2D NMR,and HR-ESI-MS data.The inhibitory effect of compounds on inflammasome activation was determined by lactate dehydrogenase(LDH)procedure.The antiproliferative activity was evaluated using MTT assay.Results:The study led to the isolation of 23 compounds,including one new compound,identified as(2Z)-3-[4-(β-D-glucopyranosyloxy)-2′-hydroxy-5′-methoxyphenyl]-2-propenoic acid(1),together with 22 known compounds recognized as 1,4-dihydro-4-oxo-3-pyridinecarbonitrile(2),methyl 4-methoxynicotinate(3),4-methoxynicotinonitrile(4),1-(3-O-β-D-glucopyranosyl-4,5-dihydroxyphenyl)-ethanone(5),neoisoastilbin(6),isoastilbin(7),aromadendrin(8),neoastilbin(9),astilbin(10),quercitrin(11),neoschaftoside(12),apigenin 6,8-bis-C-α-L-arabinoside(13),vitexin(14),bergenin(15),scopoletin(16),glucopyranoside salicyl(17),koaburside(18),benzylβ-D-glucoside(19),icariside B5(20),roseoside(21),loliolide(22),and adenosine(23).The tested compounds did not show LDH inhibition nor antiproliferative activity.Conclusion:Compound 1 was a new glycoside.Compounds 2 and 3 were obtained for the first time from natural source.The 22 known compounds constituted of alkaloids(2–4,23),phenolics(5,15,17,18),flavonoids(6–14),coumarin(16),benzyl glycoside(19),and norsesquiterpenes(20–22).All the compounds,1–23,were revealed from M.hemsleyana for the first time.This is the initial uncovering of molecules 1–10,12,13,17–19,and 23 from the genus Macaranga.The isolated compounds,11,14–16,and 20–22 established taxonomic classification of M.hemsleyana in Euphorbiaceae family.Flavonoids were outstanding as chemosystematic markers of Macaranga genus.展开更多
基金the financial support from the Natural Science Foundation of Jiangsu University of Technologythe Provincial Key Project of Natural Science Research for Colleges and Universities of Anhui Province(KJ2014A062)
文摘Ethyl 3,9-dihydroxy-9-methyl-7-phenyl-7,8,10-trihydro-6H-dibenzo[b,d]pyran-6-one-8-carboxylate(C(23)H(22)O6,Mr = 394.42) has been synthesized and its structure was determined by ~1H and ^(13)C NMR,ESI-MS,elemental analysis,and X-ray single-crystal diffraction.The crystal belongs to the triclinic system,space group P1,with a = 8.8220(17),b = 9.881(2),c = 12.157(2) A,α= 90.488(3),β= 102.664(4),γ= 98.799(3)°,V= 1020.8(3) A^3,Z= 2,Dc = 1.342 g/cm^3,μ= 0.099mm^(-1),F(000) = 436,R = 0.0615 and wR = 0.2501 for 2592 observed reflections with(I2σ(I)).In the crystal structure,the coumarin ring system is planar and the 3:4 fused cyclohexane ring adopts distorted half-chair conformation.Rich hydrogen bonding interactions are formed between compound 2 and lattice water molecules.These interactions assemble molecules of 2 into 2D layered networks in an AB stacking sequence.Its in vitro antiproliferative activities against three human cancer cell lines were evaluated by MTT assay.
基金Supported by the Natural Science Foundation of Jiangsu Province(No.BK2011088)
文摘The novel crystal of the title compound 2-(((5-(((5,7-dimethyl-[1,2,4]triazolo-[1, 5-a]-pyrimidin-2-yl)thio)methyl)-4-phenyl-4H-1,2,4-triazol-3-yl)thio)methyl)-4H-chromen-4-one methanol solvate(C27H25N7O3S2, Mr = 559.66) has been prepared and its structure was determined by single-crystal X-ray diffraction. The crystal belongs to the monocline system, space group P21/c with a = 11.9879(9), b = 14.0743(10), c = 15.9706(11)A, β = 98.509(2)°, V = 2664.9(3)A3, Z = 4, Dc = 1.395 g/cm^3, F(000) = 1168, μ = 0.116 mm-1, MoKa radiation(λ = 0.71073), R = 0.0652, and wR = 0.1425 for 5220 observed reflections with I 〉 2σ(I). X-ray diffraction analyses reveal that the molecule adopts a C-shape. The planes of the benzopyrone and triazolopyrimidine were nearly parallel to each other, with a dihedral angle of 1.21(3)°. Intramolecular and intermolecular hydrogen bonds together with π-π interations are found to exist in the structure. The results of MTT assay indicate that the title compound displays excellent antiproliferative activity against two human cancer cell lines.
基金supported by the National Natural Science Foundation of China(No.21272086)China Postdoctoral Science Foundation(No.2012T50475)the Natural Science Foundation of Jiangsu Province(No.BK2011086)
文摘The crystal structure of the new title compound 2,2-dimethyl-4-oxochroman-3-ylmorpholine-4-carbodithioate(C16H19NO3S2,Mr = 337.44) has been prepared and determined by single-crystal X-ray diffraction.The crystal is of triclinic,space group P1 with a = 9.5518(7),b = 9.7172(7),c = 11.0220(8),α = 67.08(1),β = 74.66(1),= 61.31(1)°,V = 822.72(10)3,Z = 2,Dc = 1.362 g/cm3,F(000) = 356,μ = 0.092 mm-1,MoKa radiation(λ = 0.71073),R = 0.0515 and wR = 0.1389 for 2623 observed reflections with I 2(I).X-ray diffraction analysis reveals that the chroman ring adopts a half-chair conformation while the morpholine ring shows a chair conformation.Intramolecular and intermolecular C–H···S and C–H···O hydrogen bonds together with π-π interations are found in the structure.The result of MTT assay shows the title compound displays good antiproliferative activity against two human cancer cell lines.
文摘In our efforts to identify novel potent anticancer agents, we synthesized a series of 2,7-disubstituted triazolo[1,5-a]pyrimidines (6-16). Their antiproliferative activity against Bel-7402, HT- 1080 and WI-38 cell lines was tested by MTT assay in vitro. Four of the compounds (9-11 and 16) displayed promising antiproliferative activity superior to gefitinib, especially compound 9. A preliminary SAR study of these derivatives was performed.
文摘A series of novel N-anilino-2-substituted-5-methyl-[1,2,4]triazolo[1,5-a]pyrimidine-7-amine derivatives was prepared and evaluated for their in vitro antiproliferative activity against two cancer cell lines,Bel-7402 and HT-1080.Most of the compounds inhibited the cell proliferation at a low concentration.Seven compounds,VI5,VI7,VI10,and VI12―VI15,possessed marked antiproliferative activity superior to that of cisplatin.Of these seven initial hits,compound VI10 was the most active.
文摘Many small-molecule compounds have been evaluated with potential antiproliferative activities. Ethyl 1-(phenylcarbamoyl)-2-(3,4,5-trimethoxyphenyl)cyclopropanecarboxylate, one novel cyclopropylamide analogue of combretastatin-A4(CA-4), has been synthesized and its crystal structure was characterized by X-ray single-crystal diffraction. The crystal belongs to monoclinic, space group P21/n, with a = 15.0263(3), b = 7.6574(2), c = 19.4117(4), β = 111.9010(10)o, V = 2072.36(8)3, Z = 4, C22H24NO6, Mr = 398.42, Dc = 1.277 Mg/cm3, F(000) = 844, λ(MoKα) = 1.54178 , μ = 0.770 mm–1, R = 0.0546 and wR = 0.1889 for 3319 observed reflections(I 〉 2σ(I)). Meanwhile, the compound revealed potential antiproliferative activities in several cancer cells in vitro.
基金The authors gratefully acknowledge financial support from the National Natural Science Foundation of China(Grant 30772646)the National Major Science and Technology Project of China("Innovation and Development of New Drugs",Grant 2009ZX09102-065).
文摘Cajanine,a constituent of Cajanaus cajan L.,used in traditional Chinese medicine,is a promising drug candidate because of its broad range of bioactivities.However,the total synthesis of cajanine and its derivatives has never been reported.Herein,we report the total synthesis of cajanine in nine steps with an overall yield of 10%together with its analog,longistyline A,in 8%yield.The antiproliferative activity of the two compounds against a human hepatoma cell line is also reported.
基金supported by Program for Innovative Research Team of the Ministry of Education of ChinaProgram for Liaoning Innovative Research Team in Universitythe Innovation and entrepreneurship training program for college students in Liaoning Province (No. 201410163009)
文摘A series of novel 4-substituted-phenoxy-benzamide derivatives bearing an aryl cycloaliphatic amine moiety were synthesized and evaluated for antiproliferative activity against SW620, HT29 and MGC803 cancer cell lines in vitro. The pharmacological data demonstrated that the majority of target compounds exhibited moderate efficacy in HT29 and MGC803 cell lines. Compound 10 c showed promising inhibition of hedgehog(Hh) signaling pathway in an Hh-related assay. In addition, the superposition pattern of 10 c showed a good fit for a pharmacophoric model generated by Hh inhibitors and provided a basis for further structural optimization.
基金Project supported by the Natural Science Foundation of-Zhejiang Province, China (No. Y407301).
文摘Three novel norcantharidin acylamide acids (L1 =N-thiadiazole norcantharidin acylamide acid, CIoHIlN304S; L2=N-thiazole norcantharidin acylamide acid, CjIHI2N204S and L3=N-benzothiazole norcantharidin acylamide acid, C15H14N204S) were synthesized by the reactions of norcantharidin (NCTD=7-oxabicyclo[2,2,1 ]heptane-2,3- dicarboxylic acid anhydride, C8H8O4) with 2-amino-1,3,4-thiadiazole (C2H3N3S), 2-aminothiazole (C3H4N2S) and 2-aminobenzothiazole (C7H6N2S), respectively. Their structures were characterized by elemental analysis, IR, and NMR. The inhibition rates of L3 was much higher than those of Lj and L2 against human hepatoma cells SMMC7721 cell lines in vitro. The interaction between the compounds and DNA was studied by means of fluorescence quenching studies and viscosity measurements. The emission intensities decreased obviously with increasing concentration of the compounds in the fluorescence quenching experiments. The linear Stern-Volmer quenching constant Ksq values were 0.62 (Ll), 0.55 (L2) and 1.08 (L3), respectively. The binding abilities followed the trend from high to low were L3, L1 and L2, respectively. The results of viscosity measurements showed that L1 and L2 might bind to DNA via partial intercalation, while L3 bound mainly in intercalation.
基金Supported by the Natural Science Foundation of Guangxi Province of China(No.2010GXNSFD013019), the Natural Science Fund of Education Department of Guangxi Province of China(No.201202ZD059) and the Training Project for Excellent Middle-aged/Young Teachers in Guangxi Higher Education Institutions of China.
文摘With chenodeoxycholic acid as starting material,a series of lactam derivatives of chenodeoxycholic acid was synthesized and their antiproliferative activities against some cancer cells were determined.Among the synthesized derivatives,compounds 6 and 18 displayed distinct antiproliferative activity against PC-3,H-292,SKBR3 and Hey-1B cancer cells,and compounds 10,17 and 18 showed significant antiproliferative activity against SKBR3 cells.Our results reveal that the position of hydroximino on ring A or B of the parental scaffold dramatically affects the antiproliferative activity of these compounds.The conversion of 7-hydroximino to other substituent or 7-hydroximino to 3-hydroximino in the compounds resulted in a dramatic decrease of the antiproliferative activity,suggesting the importance of 7-hydroximino group for the biological activity of the compounds.The structure/activity correlation generated from the studies provides valuable information for the further design of novel chemotherapeutic drugs.
文摘In the last years, sugar beet pectins have been the subject of several investigations involving extraction methodologies, chemical composition and functional properties. The structure of pectins, which depends on the extraction method, is decisive in their capacity to induce apoptosis on several cancer cell lines like colon, prostate and breast. In this work, sugar beet pectin extraction was performed in the following steps: lipid extraction with hexane, removal of soluble complex carbohydrates and proteins, and enzymatic treatment with amyloglucosidase, protease, and pectinase. The enzymatic treatment was carried out with Rohapect DA6L under the following conditions: 50℃, pH 4.0, 2% enzyme/substrate (E/S) ratio, 15 h, and a solid to liquid ratio of 1 : 10. The pectic extract showed a degree of polymerization (DP) profile of 55.8% with DP≥7; 4.9% with DP6; 5.8% between DP2 and DP6 ; 4.7% with DP2; and 28.8% with DP1. The pectic extract was examined for its antiproliferative activity on the MCF-7 breast cancer cell line. At a concentration range of 12.5-25 mg/mL the pectic extract killed 80.6% of the cells, exhibiting a higher antiproliferative activity than 4-hydroxytamoxifen (4- OHT), a classical anticancer drug, which killed 56.5% of the cells.
基金Supported by the Natural Science Foundation of Zhejiang Province (Y407301)
文摘A novel crystal with the molecular formula [Pd(DCA)(bipy)]2 [Pd(bipy)Cl2 ]·6.75H2O was formed by PdCl2 with disodium demethylcantharate (Na2 (DCA),DCA2= 7-oxa-bicyclo[2.2.1]heptane-2,3-bicarboxylate) and 2,2-bipyidine (bipy) through the hydrothermal method.The complex was characterized by elemental analysis and infrared spectroscopy.The structure of the complex was determined by single-crystal X-ray diffraction,which is of triclinic system,space group P1 with a=13.6818(7),b=14.8426(8),c=15.0043(8),α=97.319(3),β=92.521(3),γ=105.776(2)°,V=2898.4(3) 3,Dc=1.545 g·cm-3,Z=1,F(000)=1420,S=0.852,the final R=0.0525 and wR=0.1777 for 13634 observer reflections (I〉2σ(I)).The binding reaction of the complex with ct-DNA and bovine serum albumin (BSA) was studied by fluorescence spectroscopy.The results indicated that the complex binds to ct-DNA via the partial intercalation.The binding constant K A of the complex interaction with BSA was 3.98×10 5 L·mol-1 and one binding site would be formed.The antiproliferative activity of the complex against human hepatoma cells (SMMC7721) in vitro is much higher than that of Na 2 (DCA).
基金This project was supported by the Fogarty International Center,the National Cancer Institute,the National Institute of Allergy and Infectious Diseases,the National Institute of Mental Health,the National Institute on Drug Abuse,the National Heart Lung and Blood Institute,the National Center for Complementary and Alternative Medicine,the Office of Dietary Supplements,the National Institute of General Medical Sciences,the Biological Sciences Directorate of the National Science Foundation,and the Office of Biological and Environmental Research of the U.S.Department of Energy under Cooperative Agreement U01 TW00313 with the International Cooperative Biodiversity GroupsThis project was also supported by the National Research Initiative of the Cooperative State Research,Education and Extension Service,USDA,Grant#2008-35621-04732These supports are gratefully acknowledged.Work at Virginia Tech was supported by the National Science Foundation under Grant CHE-0722638 for the purchase of the Agilent 6220 mass spectrometer.
文摘Bioassay-guided fractionation of EtOH extracts obtained from the roots and wood of the Madagascan plant Leptaulus citroides Baill.(Cardiopteridaceae)led to the isolation of ethyl esters of three new triterpenoid saponins(1–3)and the known sesquiterpenoid cinnamosmolide(4).The structures of 1–3 were elucidated by extensive 1D and 2D NMR experiments and mass spectrometry.Compounds 1,2,and 4 showed moderate cytotoxicity against the A2780 human ovarian cancer cell line with IC50 values of 2.8,10.2 and 2.0 lM,respectively.
文摘A novel series of 5H-pyridazino[4,5-b]indoles were designed and synthesized in order to find novel potent anticancer compounds. The structures were confirmed by ^1H NMR and MS. Their antiproliferative activities against two cancer cell lines were tested by the MTT method in vitro. Three of compounds (1e, 1g, and 1h) exhibited potent antiproliferative activities, especially compound lh (with IC50 values of 5.2 μmol/L and 1.9 μmol/L against Bel-7402 and HT-1080, respectively). The preliminary structure-activity relationships of 5H-pyridazino[4,5-b]indole derivatives were discussed.
基金supported by the VK’s lab from Savitribai Phule Pune University in the form of Research Grant(No.:OSD/BCUD/392/132)
文摘Rumex nepalensis Spreng.(Polygonaceae) commonly known as Nepal Dock has wide-spectrum therapeutic potencies and is extensively used for centuries in traditional medicine systems. The leaves of this plant are edible and a rich source of natural antioxidants. They act as a possible food supplement and are largely used in pharmaceutical industry. Extracts and metabolites from this plant exhibits pharmacological activities including anti-inflammatory, antioxidant, antibacterial, antifungal, antiviral, insecticidal, purgative, analgesic, antipyretic, anti-algal, central nervous system depressant, genotoxic, wound healing and skeletal muscle relaxant activity. Due to its remarkable biological activities, it has the potential to act as a rich source of drug against life threatening diseases. However, more studies are needed to scientifically validate the traditional uses of this plant, beside isolating and identifying their active principles and characterizing the mechanisms of action. We present herein a critical account of its botany, ecology, traditional uses, phytoconstituent profile and major pharmacological activities reported in recent years and therefore will provide a source of information on this plant for further studies.
基金the support of Fundacao para a Ciência e Tecnologia(FCT),through the strategic project(No.UID/MAR/04292/2013)granted to MAREthe support from the European Union through EASME Blue Labs project AMALIA-Algae-to-MArket Lab IdeAs(No.EASME/EMFF/2016/1.2.1.4/03/SI2.750419)+1 种基金funding from European Structural&Investment Funds through the COMPETE ProgrammeNational Funds through FCT-Fundagao para a Ciência e a Tecnologia under the Programme(No.SAICTPAC/0019/2015)
文摘Osmundea pinnatifida is a red edible seaweed known as pepper dulse.O.pinnatifida was cultivated in the farm of ALGAplus(ílhavo,Portugal).This farm is integrated with a seabream and seabass commercial aquaculture and uses the nutrient-enriched water resultant from the fish production as its cultivation medium in the integrated multi-trophic aquaculture(IMTA)manner.Wild and IMTA-cultivated samples of O.pinnatifi da were screened for antioxidant and antitumor activities.The antioxidant capacity of solvent extracts from wild and IMTA cultivated samples was assessed in two methods(2,2-diphenyl-1-picrylhydrazyl(DPPH)and oxygen radical absorbance capacity(ORAC)),and their total phenolic contents(TPC)were estimated.Antitumor activity was evaluated in three different tumor cell lines(HepG-2,MCF-7,and SH-SY5Y)through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT)assay.Among the solvents used for extraction,dichloromethane was the most eff ective to extract phenolic compounds and presented higher ORAC.A significant correlation was found between TPC and ORAC,which was also sustained by the principal components analysis(PCA).Dichloromethane extracts induced a cytostatic eff ect on MCF-7 cells and showed weak cytotoxicity to SH-SY5Y cells and weak impact on cell proliferation.Overall,there were no statistically signifi cant differences in the biological activities shown by the wild and IMTA-cultivated samples.Hence,O.pinnatifida can be obtained in an economical and environmentally sustainable way through IMTA,maintaining bioactive properties in a high potential for further nutraceutical purposes.
基金Supported by the National Major Scientific and Technological Special Project of China(No.2011ZX09501-001)
文摘Histone deacetylases(HDACs) are considered to be among the most promising targets for the development of anti-cancer drugs,and HDAC inhibitors(HDACIs) have become a promising class of anti-cancer drugs.To explore whether thioacetyl group as the zinc binding group(ZBG) and a slight change in the hydrophobicity of the recognition domain of HDACIs could alter their activities,we synthesized a series of cyclo[-L-Am7(SAc)-Aib-L-Phe(n-Cl)D-Pro-] and evaluated their HDAC-inhibitory and antiproliferative activities.The results show that these peptides could inhibit HDAC at 10-9 mol/L level,and could selectively inhibit the proliferation of three human cancer cell lines with IC 50 at 10-6 mol/L level.Docking study was conducted to examine the mechanisms by which these peptides interact with HDAC2.It appeared that a zinc ion in the active site of HDAC was coordinated by the carbonyl oxygen atom of the ZBG in the inhibitor.Both the ZBG domain of all the peptides and the surface recognition domain of cyclo[-L-Am7(SAc)-Aib-L-Phe(o-Cl)-D-Pro-] and that of cyclo[-L-Am7(SAc)-Aib-L-Phe(m-Cl)-D-Pro-] interacted with HDAC2 via hydrogen bonding.Hydrophobic interaction has been considered to provide favorable contributions to stabilizing the complexes,and the introduction of a chlorine atom at the aromatic ring on the L-Phe position of these peptides affected the interaction between each of these inhibitors and the enzyme,resulting in slight change in the structure of the surface recognition domain of the peptides.
基金Supported by the National Natural Science Foundation of China(Nos.J1210040, 21173074).
文摘Twenty prenylated flavonoids 1-20 were synthesized by glycoside hydrolysis, dehydrogenation, selective O-methylation, O-prenylation and Claisen rearrangement reaction, from abundant and inexpensive natural flavonoids naringin, hespiredin, quercetin and myricetin. Among them, 1-7, 10-15 and 17-20 are novel compounds, the natural product 3,3',4',7-tetramethoxy-8-prenyl-5-hydroxy flavonoid(16) was synthesized in a high yield. Their antiprolirative activities were evaluated in vitro on a panel of three human cancer cell lines(HeLa, HCC1954 and SK-OV-3). The results show that most of the target compounds displayed moderate to potent antiprolirative activities against the three cancer cells with half maximal inhibitory concentration(ICs0) values from 0.49 μmol/L to 95.07 μmol/L. Among them, 3′,4′,7-trimethoxyl-5-hydroxyl-8-prenyl flavonoid(12) exhibited the strongest antiprolirative activity against the three cancer cells mentioned above with IC50 values of 0.91-7.08 μmol/L. 3′,7-Dimethoxy-5-O- prenyl flavone(6) and 3′,4′,7-trimethoxy-5-O-prenyl flavone(10) showed selective antiproliferative activity against HCC1954 cells with TC50 value of 0 49 and 5 .32μmol/L, respectively.
基金financially supported by the National Natural Science Foundation of China(No.U1906213)the National Key Research and Development Program of China(No.2022YFC2804100)。
文摘Four new cyclohexapeptides,pyridapeptides F–I(1–4),were isolated from the fermentation broth of marine sponge-derived Streptomyces sp.OUCMDZ-4539.The pyridapeptides F–H(1–3)are composed ofβ-hydroxyleucine,alanine,O-methylthreonine,hexahydropyridazine-3-carboxylic acid,5-hydroxytetrahydropyridazine-3-carboxylic acid,and(2S,3R,4E,6E)-2-amino-3–hydroxy-4,6-dienoic acid residues.Pyridapeptide I(4)contains(2S,3R,4E,6E)-2-amino-3–hydroxy-8-methylnona-4,6-dienoic acid residue and a very rare glycose residue,aculose.Their structures were determined based on spectroscopic analysis and chemical methods.Pyridapeptides G–I(2–4)have the 2,3,6-trideoxyhexose units glycosylated at theγ-OH-TPDA residue,displayed significant antiproliferative activity against four(PC9,MKN45,Hep G2,K562)or two(PC9,MKN45)human cancer cell lines.
基金supported by the National Natural Science Foundation of China(No.81860615,82260682)Project of Yunnan Characteristic Plant Screening and R&D Service CXO Platform(No.2022YKZY001).
文摘Objective:To study constituents of the leaves of Macaranga hemsleyana,and evaluate their inhibitory effects against NOD-like receptor thermal protein domain associated protein 3(NLRP3)inflammasome activation,and antiproliferative activity.Methods:The constituents were isolated and purified by column chromatography on MCI gel CHP20P/P120,silica gel,Sephadex LH-20,and HPLC.The structures of compounds were determined by 1D,2D NMR,and HR-ESI-MS data.The inhibitory effect of compounds on inflammasome activation was determined by lactate dehydrogenase(LDH)procedure.The antiproliferative activity was evaluated using MTT assay.Results:The study led to the isolation of 23 compounds,including one new compound,identified as(2Z)-3-[4-(β-D-glucopyranosyloxy)-2′-hydroxy-5′-methoxyphenyl]-2-propenoic acid(1),together with 22 known compounds recognized as 1,4-dihydro-4-oxo-3-pyridinecarbonitrile(2),methyl 4-methoxynicotinate(3),4-methoxynicotinonitrile(4),1-(3-O-β-D-glucopyranosyl-4,5-dihydroxyphenyl)-ethanone(5),neoisoastilbin(6),isoastilbin(7),aromadendrin(8),neoastilbin(9),astilbin(10),quercitrin(11),neoschaftoside(12),apigenin 6,8-bis-C-α-L-arabinoside(13),vitexin(14),bergenin(15),scopoletin(16),glucopyranoside salicyl(17),koaburside(18),benzylβ-D-glucoside(19),icariside B5(20),roseoside(21),loliolide(22),and adenosine(23).The tested compounds did not show LDH inhibition nor antiproliferative activity.Conclusion:Compound 1 was a new glycoside.Compounds 2 and 3 were obtained for the first time from natural source.The 22 known compounds constituted of alkaloids(2–4,23),phenolics(5,15,17,18),flavonoids(6–14),coumarin(16),benzyl glycoside(19),and norsesquiterpenes(20–22).All the compounds,1–23,were revealed from M.hemsleyana for the first time.This is the initial uncovering of molecules 1–10,12,13,17–19,and 23 from the genus Macaranga.The isolated compounds,11,14–16,and 20–22 established taxonomic classification of M.hemsleyana in Euphorbiaceae family.Flavonoids were outstanding as chemosystematic markers of Macaranga genus.