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1.
The reaction of 6′-chloro-6′-deoxyraffinose deca-acetate with a variety of nucleophilic anions (Br-,I-,N-3) gave the corresponding 6′-substituted raffinoses. The 6′-azide was further converted into 6′-amino-6′-deoxyraffinose, isolated as its N-acetyl derivative, and silver fluoride-induced elimination of hydrogen iodide from the 6′-iodide gave the 6′-deoxy-5′-ene. Treatment of 6′-chloro-6′-deoxyraffinose and 6′,6″-dichloro-6′,6″-dideoxyraffinose with base afforded, respectively, 3′,6′-anhydro-and 3′,6′;3″,6″-dianhydro-raffinose in high yields. In addition, the dichloride was converted into 6′,6″-diazido-6′,6″-dideoxyraffinose.  相似文献   

2.
The interaction between tetramethylcucurbit[6]uril (host) and 5,5'-dimethyl-2,2'-bipyridyl hydrochloride (guest) was studied by 1H NMR, X-ray crystallography, electronic absorption spectroscopy, fluorescence emission spectra and quantum chemistry calculations. This experimental-computational study that indicated the host can orientationally encapsulate the guest with a moderate association constant value. Computation qualitatively explained the split UV-visible absorption peak of the inclusion complex.  相似文献   

3.
4,4′-Diisothiocyano-1,2-diphenylethane-2,2′-disulfonic acid (H2DIDS) known as an irreversible inhibitor of the anion transport in red blood cells (Cabantchik, Z.I. and Rothstein, A. (1972) J. Membrane Biol. 10, 311–330) blocks also the uptake of bile acids and of some foreign substrates in isolated hepatocytes (Petzinger, E. and Frimmer, M. (1980) Arch. Toxicol. 44, 127–135). [3H]H2DIDS was used for labeling of membrane proteins probably involved in anion transport of rat liver cells. The membrane proteins modified in vitro by [3H]H2DIDS were compared with those labeled by brominated taurodehydrocholic acid. The latter is one of a series of suitable taurocholate derivatives, all able to bind to defined membrane proteins of hepatocytes and also known to block the uptake of bile acids as well as of phallotoxins and of cholecystographic agents (Ziegler, K., Frimmer, M., Möller, W. and Fasold, H. (1982) Naunyn-Schmiedeberg's Arch. Pharmacol. 319, 254–261). The radiolabeled proteins were compared after SDS-electrophoresis with and without reducing agent present, solubilization by detergents, two-dimensional electrophoresis and after separation of integral and peripheral proteins. Our results suggest that the anion transport system of liver cells cannot distinguish between bile acids and the anionic stilbene derivative (DIDS). The labeling pattern for both kinds of affinity labels was very similar. Various combinations of separation techniques gave evidence that the radiolabeled membrane proteins are not subunits of a single native channel protein.  相似文献   

4.
Starting from the previously describedtert-butyl esters of 4-epimericN-benzyloxycarbonyl-4-hydroxyprolines andN-benzyloxycarbonyl-4-trans- and 4-cis-trifluoroacetaminoprolinetert-butyl esters, the corresponding uprotected 4-aminoprolines and a number of their partially protected derivatives were synthesized via the intermediate 4-O-mesyl and 4-azide derivatives. The reductive amination ofN-benzyloxycarbonyl-4-oxoprolinetert-butyl ester with ammonium acetate led toN-benzyloxycarbonyl-4-cis-4′-cis- and 4-cis-4′-trans-diprolinylamines. The1H NMR and CD spectra of the synthesized compounds are described.  相似文献   

5.
As a part of systematic investigation of synthesis and biological activities of indole analogues linked to various heterocyclic systems, we have synthesized new compounds viz., 2-amino-4-(5′-substituted 2′-phenyl-1H-indol-3′-yl)-6-aryl-4H-pyran-3-carbonitriles (2ai), 4,5-diamino-6-(5′-substituted 2′-phenyl-1H-indol-3′-yl)-8-aryl-2-oxo-2,6-dihydrodipyrano [2,3-b:3,2-e]pyridine-3-carbonitriles (3ai), 4-amino-5-(5′-substituted 2′-phenyl-1H-indol-3-yl)-7-aryl-1H-pyrano[2,3-d]pyrimidin-2(5H)-ones (4ai), 4-amino-5-(5′-substituted 2′-phenyl-1H-indol-3′-yl)-7-aryl-1H-pyrano[2,3-d]pyrimidin-2(5H)-thiones (5ai), 4-(5′-subtituted 2′-phenyl-1H-indol-3′-yl)-6-aryl-1,4-dihydropyrano[2,3-c]pyrazol-3-amines (6ai) and 5-(5′-substituted 2′-phenyl-1H-indol-3′-yl)-7-aryl-3H-pyrano[2,3-d]pyrimidin-4(5H)-ones (7ai). Antibacterial activity results revealed that, compound 6a showed promising activity versus Escherichia coli, Staphylococcus aureus and Klebsiella pneumoniae. Compound 6d exhibited good activity against S. aureus, K. pneumoniae and Pseudomonas aeruginosa. Antifungal activity results indicated that, compound 4d exhibited maximum zone of inhibition against Aspergillus oryzae and Aspergillus flavus. In case of antioxidant activity, compound 4a showed promising radical scavenging activity, ferric ions (Fe3+) reducing antioxidant power (FRAP) and metal chelating activity.  相似文献   

6.
In an attempt to find the effective phytopesticides, eight novel 4′-substituted benzenesulfonate derivatives of 4-deoxypodophyllotoxin were synthesized and preliminarily tested against the pre-third-instar larvae of Mythimna separata Walker in vivo at the concentration of 1 mg/mL. Among all of the tested analogs, compounds 5a, 5c, 5d, and 5h showed the higher insecticidal activity than 4-deoxypodophyllotoxin. Especially 5a exhibited the most potent insecticidal activity compared with toosendanin, a commercial insecticide derived from Melia azedarach.  相似文献   

7.
8.
The syntheses of two potential cAMP affinity lables, 1,N 6-(3-iodopropyleno)adenosine 3′,5′-cyclic-monophosphate and 2′-O-(2-iodo-3-hydroxypropyl) adenosine 3′,5′-cyclic-monophosphate, by a two-step chemical procedure are described. TheN 6- and 2′-O-allyl intermediates were prepared selectively by alkylation of cAMP in organic and alkaline aqueous solutions, respectively. Treatment of theN 6-allyl derivative withN-iodosuccinimide resulted in iodine addition to the double bond and cyclization to theN 1 position of the purine ring. The iodohydrin analog was synthesized by reaction of 2′-O-allyl-cAMP with potassium iodide and thallium trichloride in acetate buffered solution. The products were isolated by column chromatography and characterized by thin-layer chromatography, elemental analysis, and ultraviolet,13C, and1H NMR spectroscopy. The cAMP analogs were found to react with lysine and cysteine. Both cAMP derivatives were tested for their reaction with the low-K m cAMP phosphodiesterase of human platelets. The ribose-substituted analog functioned as a competitive inhibitor (K I =0.72 μM) and caused a time-dependent irreversible inactivation of the phosphodiesterase. In contrast, the purine-substituted derivative acted neither as a reversible competitive inhibitor nor as an irreversible inactivator of the enzyme. These results indicate the specificity of these potential cAMP analogs in their interaction with the phosphodiesterase.  相似文献   

9.
The capacity of non-illuminated nephrotoxin orellanine ([2,2′-bipyridine]-3,3′,4,4′-tetrol-1,1′-dioxide) to induce DNA damage in the presence of ferrous iron and dioxygen has been evaluated. Maximal single-strand breaks in plasmid DNA were obtained with a metal to ligand ratio 1:3. Instantaneous oxidation of Fe2+ in presence of orellanine under air was responsible for oxy-radical production concomitant to a stable ferric complex Fe(III)Or3 formation, leading to oxidative DNA breakage at physiological pH. DNA damage was lowered in the presence of SOD and catalase or DMSO, indicating a set of reactions that leads to oxyradical generation. Iron chelators such as DTPA and EDTA had no protecting effect, Desferal slightly protected. GSH acted as an oxy-radical scavenger, whereas cysteine induced stronger damage.

Closely related bipyridine compounds were also studied in presence of Fe2+ and O2 using a combination of spin-trapping and DNA-nicking experiments, none of which were able to chelate iron and induce damage at pH 7. Both catecholic moieties and aminoxide groups are required for observing breakage at physiological pH.  相似文献   

10.
Insecticide resistance has limited the number of available chemical options for insect pest control. Hence there is a need for new chemistries with novel modes of action. Here we investigate the mode of action for an insecticide that has not yet been released for commercial use. The ovicidal, larvacidal and adulticidal effects of 5,5′-dimethyl -2, 2′-dipyridyl (termed Ha44), which is being developed as a treatment for head lice, were evaluated in the Drosophila melanogaster model system. Ha44 demonstrated significant activity against embryos and was capable of arresting development at a number of stages of embryogenesis. The effects of Ha44 on embryos was shown to be reversible following the addition of the metal ions Fe(II) and Fe(III), Cu and Zn. When larvae were exposed to Ha44, lethality was recorded at similar concentrations to those observed for embryos. Using an eYFP reporter system it was shown that Ha44 was able to reduce the levels of both copper and zinc in the digestive tract, confirming the binding of Ha44 to these metals in vivo. Ha44 has further been shown to inhibit a zinc containing metalloproteinase in vitro. Exposure of adult flies to Ha44 resulted in lethality, but at higher concentrations than those observed for embryos and larvae. The median lethal dose in adult flies was shown to be associated with the type of exposure, with an LD-50 of 1.57 mM being recorded following the direct contact of flies with Ha44, while an LD-50 of 12.29 mM was recorded following the ingestion of the compound. The capacity of Ha44 to act on all stages of the life-cycle and potentially via a range of targets suggests that target site resistance is unlikely to evolve.  相似文献   

11.
The need of long-term treatment for chronic HBV, emergence of drug-resistant viruses and inefficiency of currently approved therapies to eliminate covalently closed circular DNA (cccDNA), mandates identification of potent and selective inhibitors of HBV replication with novel mechanisms of action. Entecavir, a carbocyclic guanosine nucleoside analog, is the most potent inhibitor of HBV replication on the market. Moreover, the naturally occurring carbocyclic nucleosides aristeromycin are known for their wide range of antiviral activities.

In this research, we have utilized BINAP directed rhodium catalyzed reductive carbocyclization of 1,6-enynes (8a–b) through asymmetric hydrogenation which is an approach, not yet explored in carbocyclic sugar synthesis. Interestingly, we obtained exclusive anti-(9a) and Z-anti (9b) carbocyclic sugars. The new aristeromycin analogs (10a–b) with scaffold combination of entecavir and aristeromycin were then synthesized using the Mitsunobu reaction followed by deprotection.  相似文献   


12.
The mutagenicity and DNA-binding affinity of members of a series of acridine-substituted derivatives of 4′-(9-acridinylamino)methanesulphonanilide (AMSA) have been compared. The series includes compounds ranging from highly active to inactive in the L1210 murine leukaemia. Binding to DNA was measured by an ethidium displacement technique, with a correction being made for acridine-induced quenching of ethidium. Mutagenicity was assessed by measuring the reversion frequencies of the frameshift tester strain Salmonella typhimurium TA1537 in liquid culture. The results indicate that maximum mutagenicity is found in a “window” of DNA-binding affinities between 106 and 5 × 106 M?1 (determined at 0.01 ionic strength). Compounds with binding affinities below 106 M?1 generally lacked both antitumour and mutagenic activity, whereas those with affinities above 5 × 106 M?1 were active against L1210 leukaemia but virtually inactive in inducing frameshift mutations.  相似文献   

13.
Resveratrol (3,4′,5-trihydroxystilbene, RV) exerts remarkable cytostatic and cytotoxic effects against a multitude of human cancer cell lines. Since the introduction of additional hydroxyl groups was supposed to increase the biological activity of RV, we have synthesized a number of polyhydroxylated stilbene analogues as potential antitumor agents. In this study, the activity of 3,3′,4,4′,5,5′-hexahydroxystilbene (M8) was investigated in HL-60 human promyelocytic leukemia cells. Employing a growth inhibition assay, incubation with M8 and RV resulted in IC50 values of 6.25 and 12 μM, respectively. Using a specific Hoechst/propidium iodide double staining method, we found that M8 was able to induce apoptosis in concentrations significantly lower than those of RV. In addition, M8 arrested cells in the S phase and totally depleted cells in the G2-M phase of the cell cycle (143% and 0% of control after treatment with 12.5 μM M8, respectively). We therefore believe that this promising agent deserves further preclinical and in vivo testing.  相似文献   

14.
1. The reactions of 2,2'- and 4,4'-dipyridyl disulphide (2-Py-S-S-2-Py and 4-Py-S-S-4-Py) with l-ergothioneine (2-mercapto-l-histidine betaine), 2-mercaptoimidazole, 1-methyl-2-mercaptoimidazole, thiourea, thioacetamide, 2-thiopyridone (Py-2-SH) and 4-thiopyridone (Py-4-SH) were investigated spectrophotometrically in the pH range approx. 1-9. 2. These reactions involve two sequential reversible thiol-disulphide interchanges. 3. The reaction of l-ergothioneine with 2-Py-S-S-2-Py and/or with the l-ergothioneine-Py-2-SH mixed disulphide, both of which provide Py-2-SH, is characterized by at least three reactive protonic states. This provides definitive evidence that neutral l-ergothioneine is a reactive nucleophile, particularly towards the highly electrophilic protonated disulphides. 4. A similar situation appears to obtain in the reactions of l-ergothioneine and Py-2-SH with 4-Py-S-S-4-Py and in the reactions of the other 2-mercaptoimidazoles, thiourea and Py-4-SH with 2-Py-S-S-2-Py. The nucleophilic reactivity of Py-4-SH suggests that general base catalysis provided by the disulphide in a cyclic or quasi-cyclic transition state is not necessary to generate nucleophilic reactivity in the other amino-thiones whose geometry could permit such catalysis. 5. The existence of a positive deuterium isotope effect in the l-ergothioneine-2-Py-S-S-2-Py system at pH6-7 provides no evidence for general base catalysis but is in accord with a mechanism involving specific acid catalysis and post-transition-state proton transfer. 6. The pH-dependences of the overall equilibrium positions of the various thiol-disulphide interchanges are described. 7. Reaction of thioacetamide with a stoicheiometric quantity of 2-Py-S-S-2-Py at pH1 provides 2 molecules of Py-2-SH per molecule of thioacetamide and elemental sulphur; these findings can be accounted for by thiol-disulphide interchange to provide a thioacetamide-Py-2-SH mixed disulphide followed by fragmentation to provide CH(3)CN, S and Py-2-SH. 8. Provision of high reactivity in the neutral forms of the members of this series of sulphur nucleophiles by electron donation by the amino group is compared with the well known alpha effect that provides enhanced nucleophilicity in compounds containing an electronegative atom adjacent to the nucleophilic atom. 9. The decrease in the u.v. absorption of l-ergothioneine at 257nm consequent on transformation of its aminothione moiety into an S-alkyl-2-mercaptoimidazole moiety provides a convenient method of following the alkylation of l-ergothioneine by iodoacetamide. 10. The pH dependence of the extinction coefficient of l-ergothioneine at 257nm is described by epsilon(257)={8x10(3)/(1+K(a)/[H(+)]} +6x10(3)m(-1).cm(-1) in which pK(a)=10.8. 11. In the pH range 3-11 the reaction is characterized by two reactive protonic states (X and XH). 12. The X state, reaction of the ionized 2-mercaptoimidazole moiety of the l-ergothioneine dianion with neutral iodoacetamide, is characterized by the second-order rate constant 4.0m(-1).s(-1) (25.0 degrees C, I=0.05). The XH state, characterized by the second-order rate constant 0.03m(-1).s(-1), is interpreted as reaction of the thione form of the neutral 2-mercaptoimidazole moiety of the l-ergothioneine monoanion with neutral iodoacetamide. 13. The XH state of the alkylation reaction does not exhibit a deuterium isotope effect.  相似文献   

15.
Abstract

The deuterations of 2′-deoxyguanosine in the 4′ and 5′ positions have been described elsewhere (1). The starting material is the 5′-aldehyde formed by mild oxidation with N,N-dicyclohexyl carbodiimide in dimethyl sulphoxide of the fully protected nucleoside with free 5′-alcoholic function. The 5′4euteration was achieved by reduction with deuterated sodium borohydride. Incorporation of deuterium in the 4′-position was achieved v i a an enhanced keto-enol tautomerim by heating the aldehyde in 50/50 D20/pyridine, with subsequent reduction of the aldehyde with NaBH4. The 6-furanoid form was isolated from the I-lyxo by-product by reverse phase HPLC. Applied to pyrimidine 2′-deoxyribonucleosides, this method was shown to give deuterated 2′-deoxycytidine and thymidine in good yield.  相似文献   

16.
5-(4??-substituted phenylazo)-2-thioxothiazolidinone derivatives (HLn) have been synthesized and characterized by elemental analysis, spectra (IR, electronic and 1H NMR). The IR spectral data indicate that the compounds can exist in two resonance structures. The synthesized ligands were screened for their antimicrobial activity against four bacterial species, two Gram positive bacteria (Bacillus cereus and Staphylococcus aureus) and two Gram negative bacteria (Escherichia coli and Klebsiella pneumoniae) as well as against some species various of fungi; Aspergillus niger, Penicillium chrysogenum, Penicillium italicum and Fusarium oxysporium. The results showed that most these ligands are good antibacterial agents against B. cereus and S. aureus and antifungal agents against A. niger and F. oxysporium. HL3 was found to be the most effect compound against all tested microorganisms. The size of clear zone were ordered as follows p-(OCH3?<?CH3?<?H?<?Cl?<?NO2) as expected from Hammett??s constant ??R.  相似文献   

17.
  • 1.1. 3,3′,4,4′-Tetrachlorobiphenyl (TCB) was 20–100 times more toxic in chick embryos than in turkey embryos when injected into eggs.
  • 2.2. The ed50-value for induction of AHH activity by TCB in the liver of early chick and turkey embryos was estimated to be 0.6 and 6 μg/kg egg, respectively.
  • 3.3. In both species α-naphthoflavone was more effective than metyrapone at inhibiting basal and TCB-induced AHH activities.
  • 4.4. The TCDD receptor was detected in the liver of 7-day-old chick embryos, while it was not found in 9-day-old turkey embryo liver.
  相似文献   

18.
Neuregulin 1 (Nrg1) functions in neuronal migration, survival and differentiation as well as synaptogenesis during ontogenetic development and maintenance of synaptic functions in the adult mammalian brain. The neural adhesion molecule L1 (L1CAM) functions in similar overlapping, but also non-overlapping roles in the nervous system. In the present study, we therefore investigated some aspects of the functional relationship between Nrg1 and L1 in mammalian neural cells. Nrg1 regulates the expression of L1 in cultures of both human neuroblastoma SK-N-SH cells and mouse cortical and hippocampal neurons. To analyze the role of Nrg1 on L1 expression in vivo, young adult male mice received intraperitoneal injections of Nrg1 or PBS (vehicle control). The correlation between Nrg1 and L1 expression was tested by qPCR, Western blot analysis, and immunocytology. Our data indicate that neuregulin 1-β (Nrg1β) increases L1 expression in neurons of the cerebral cortex, and decreases expression in neurons of the hippocampus in vitro and in vivo. In addition, Nrg1 induces phosphorylation of its receptors, ErbB2 and ErbB4, the predominant ErbB receptors in the nervous system. These results show that Nrg1β affects expression of L1 in the central nervous system and in parallel activates the ErbB receptors for Nrg1, suggesting a crosstalk between molecules that are of prime importance for nervous system functions.  相似文献   

19.
《Carbohydrate research》1986,154(1):93-101
O-β-d-Galactopyranosyl-(1→4)-O-[α-l-fucopyranosyl-(1→3)]-d-glucose has been synthesised by reaction of benzyl 2,6-di-O-benzyl-4-O-(2,3,4,6-tetra-O-benzyl-β-d-galactopyranosyl)-β-d-glucopyranoside with 2,3,4-tri-O-benzyl-α-l-fucopyranosyl bromide in the presence of mercuric bromide, followed by hydrogenolysis. Benzylation of benzyl 3′,4′-O-isopropylidene-β-lactoside, via tributylstannylation, in the presence of tetrabutylammonium bromide or N-methylimidazole, gave benzyl 2,6-di-O-benzyl-4-O-(6-O-benzyl-3,4-O-isopropylidene-β-d-galactopyranosyl)-β-d-glucopyranoside (6). α-Fucosylation of 6 in the presence of tetraethylammonium bromide provided either benzyl 2,6-di-O-benzyl-4-O-[6-O-benzyl-3,4-O-isopropylidene-2-O-(2,3,4-tri-O-benzyl-α-l-fucopyransoyl)-β-d- galactopyranosyl]-β-d-glucopyranoside (13, 73%) or a mixture of 13 (42%) and benzyl 2,6-di-O-benzyl-4-O-[6-O-benzyl-3,4,-O-isopropylidene-2-O-(2,3,4-tri-O-benzyl-α-l-fucopyranosyl)-β-d- galactopyranosyl-3-O-(2,3,4-tri-O-benzyl-α-l-fucopyranosyl)-β-d-glucopyranoside (16, 34%). α-Fucosylation of 13 in the presence of mercuric bromide and 2,6-di-tert-butyl-4-methylpyridine gave 16 (73%). Hydrogenolysis and acid hydrolysis of 13 and 16 afforded O-α-l-fucopyranosyl-(1→2)-O-β-d-galactopyranosyl-(1→4)-d-glucose and O-α-l-fucopyranosyl-(1→2)-O-β-d-galactopyranosyl-(1→4)-O-[α-l-fucopyranosyl-(1→3)]-d-glucose, respectively.  相似文献   

20.
Based on the discovery of thymine as an ecdysteroid agonist, a series of 1,4-disubstituted diacylhydrazine derivatives with a thymine moiety were designed and synthesized. The activities of these compounds against Spodoptera litura (Fabricius) were evaluated by the insect immersion method. Results showed that compound 2h with an N-cyclohexylmethyl substituent exhibits the most potent agonist activity with a median lethal concentration of 23.21 μg/mL. This compound also caused malformation of molting larvae and adults. Compound 2h was further demonstrated as an ecdysteroid agonist by reporter gene assay on the Spodoptera frugiperda cell line (Sf9 cells). A molecular docking study indicated that hydrophobic interactions and the formation of hydrogen bonds between the compounds and the ecdysone receptor play critical roles in promoting the binding affinity of the compound. The structure of compound 2h may serve as a favorable template for the development of new ecdysteroid agonists with a pyrimidinedione moiety.  相似文献   

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