Synthesis and antitumor evaluation of C3/C3 fluoroquinolone dimers(Ⅰ):Tethered with a fused heterocyclic s-triazolo[2,1-b][1,3,4]thiadiazole

<正>Five C3/C3 fluoroquinolone dimers tethered with a fused heterocyclic ring of s-triazolo[2,1-b][1,3,4]thiadiazole derived from antibacterial quinoiones were synthesized and characterized,and their in vitro antitumor activity against L1210,CHO cell lines was evaluated via the respective IC_(50) values.     

Synthesis and Molecular Structure of 1,5-Diphenyl-3-phenacylthio-1H-1,2,4-triazole

1 INTRODUCTION 1,2,4-Triazole and its derivatives are very useful compounds due to their broad spectrum of pharmacological activities, such as antitumor[1], antiviral[2 ～ 4], antibacterial[5] and antifungal[6] activities. Moreover, they can be used as ver- satile ligands for transition metals. Particularly, they exhibit a strong and typical property of act- ing as bridging ligands between two metal cen- ters[7, 8]. 3-Substituted thio-1H-1,2,4-triazole is the important 1,2,4-triazole deri…     

Synthesis and antitumor and antibacterial evaluation of fluoroquinolone derivatives(Ⅲ):Mono- and bis-Schiff-bases

To further explore an efficient modified route for the shift from an antibacterial fluoroquinolone to an antitumor one,mono-Schiff bases 6a-6h related to ciprofloxacin C3 carbonylhydrazone and bis-Schiff bases 4a-4h corresponding to C3/C7 carbonylhydrazone/hydrazone attached on a skeleton of ciprofloquinolone were designed and synthesized,and their in vitro antitumor activity against CHO,HL60,L1210 cells and antibacterial activity against Staphylococcus aureus and Escherichia coli were also reported.     

Synthesis and antibacterial activity of novel [1,2,4]triazolo [3,4-h][1,8]naphthyridine-7-carboxylic acid derivatives

Novel tricyclic fluoroquinolones,[1,2,4]triazolo[3,4-h][1,8]naphthyridine-8-one-7-carboxylic acid derivatives 4a-4h bearing carrying a functional Mannich-base moiety at the C-8 position,were synthesized and evaluated for their antimicrobial activity.The results showed that some compounds with a piperazine side chain exhibited comparable or better antibacterial activity than comparator cirprofloxacin.Furthermore,the targeted compounds also displayed a broad spectrum of activity against resistant strains including both Gram-negative and Gram-positive bacteria.In particular,compound 4h showed an MIC of 0.25 μg/mL in antibacterial assay against multiple drug-resistant Escherichia coli,which represents an about 30-fold increase of potency compared to ciprofloxacin.Thus,their excellent antibacterial activity against resistant strains suggests that triazole-fused fluoroquinolones warrant further optimization as novel anti-infective chemotherapies.     

Synthesis and Antibacterial Activity of 8-Substituted Phenyl-1-pyridin-3-yl-5H-bis[1, 2, 4]triazolo[3, 4-b； 4＇, 3＇-d][1, 3, 4] thiadiazines

To find new structural leading compounds for the research of the multidrug resistant of antibacterial agents, five novel 8-substituted phenyl-l-pyridin-3-yl-5H-bis[1, 2, 4] triazolo[3, 4-b;4‘,3‘-d] thiadiazines were prepared from the corresponding intermediates of 3-(5-substituted phenyl[1,3,4]oxadiazol-2-ylmethylsulfanyl)-5-pyridin-3-yl-[1,2,4]triazol-4-ylamines via intramolecular cyclization and the antibacterial activity in vitro against Gram-postive (G^ ) and Gramnegatiye (G) bacteria was primarily evaluated.     

The physicochemical properties of some imidazolium-based ionic liquids and their binary mixtures

The density, viscosity and conductivity of ionic liquids (ILs), 1-octyl-3-methylimidazolium tetrafluoroborate ([omim][BF4]), 1-octyl-3-methylimidazolium chloride ([omim][Cl]), 1-hexyl-3-methylimidazolium tetrafluoroborate ([hmim] BF4]), 1-hexyl- 3-methylimidazolium chloride ([hmim][Cl]), 1-hexyl-3-methylimidazolium hexafluorophosphate ([hmim][PF6]), and the [omim][BF4] + [omim][Cl], [hmim][BF4] + [hmim][Cl], and [hmim][PF6] + [hmim][Cl] binary mixtures were studied at dif- ferent temperatures. It was demonstrated that the densities of both the neat ILs and their mixtures varied linearly with temper- ature. The density sensitivity of a binary mixture is between those of the two components. The excess molar volumes (VE) of [hmim][BF4] + [hmim][Cl] and [hmim][PF6] + [hmim][Cl] mixtures are positive in the whole composition range. For [omim][BF4] + [omim][Cl], the VE is also positive in the [omim][Cl]-rich region, but is negative in the [omim][BF4]-rich re- gion. The viscosity or conductivity of a mixture is in the intermediate of those of the two neat ILs. For all the neat ILs and the binary mixtures studied, the order of conductivity is opposite to that of the viscosity. The Vogel-Tammann-Fulcher (VTF) equations can be used to fit the viscosity and conductivity of all the neat ILs and the binary mixtures. The neat ILs and their mixtures obey the Fractional Walden Rule very well, and the values of the Walden slopes are all smaller than unit, indicating obvious ion associations in the neat ILs and the binary mixtures.     

Synthesis and electrochemical properties of 2,6-bis（6-aryl-[1,2,4]- triazolo[3,4-b][1,3,4]-thiadiazole-3-yl）pyridines

By the condensation of 2,6-bis（4-amino-5-mercapto-[1,2,4]-triazoles-2）pyridine with aromatic acid in the presence of phosphorus oxychloride. Compounds of 2,6-bis（6-aryl-[1,2,4]-triazolo[3,4-b][1,3,4]-thiadiazole-3-yl）pyridines were synthesized. Their structures were confirmed by IR, ^1H NMR spectroscopies and elemental analysis. Their electrochemical behavior and cyclic voltammogram also were be studied. The results showed that they have high ionization potentials and good affinity.     

A series of naphthalimide azoles: Design, synthesis and bioactive evaluation as potential antimicrobial agents

A series of naphthalimide azoles as potential antibacterial and antifungal agents were conveniently and efficiently synthesized starting from commercially available 6-bromobenzo[de]isochromene-1,3-dione. All the new compounds were characterized by NMR, IR, MS and HRMS spectra. Their antimicrobial activities were evaluated against four Gram-positive bacteria, four Gram-negative bacteria and two fungi using two-fold serial dilution technique. The biological assay indicated that most of the prepared compounds exhibited inhibition to the tested strains. In particular, the triazolium derivatives not only gave higher efficacy than their corresponding precursory azoles, but also demonstrated comparable or even better potency than the reference drugs Chloromycin, Orbifloxacin and Fluconazole. Some factors including structural fragments, pH and ClogP values of the target molecules were also preliminarily discussed.     

Synthesis and Antibacterial Activities of Erythromycin Derivatives

Ten new erythromycin antibacterial agents containing amidino group were designed and synthesized from erythromycin via oximation, reduction and condensation. Their structures were confirmed by MS and ^13C NMR; the synthetic condition(reaction medium)was explored; and their in vtiro antibacterial activities were tested. Compound HMA-3 showed antibacterial activity against staphylococcus aureus, which is equivalent to that of erythromycin A. Compounds HMA-8 and HMA-4 also showed an antibacterial activitiy. But no compound showed bactericidal activity.     

INFLUENCE OF MOLECULAR WEIGHT AND PERIODATE-MODIFICATION OF β-D-GLUCANS FROM PORIA COCOS SCLEROTIUM ON ANTITUMOR ACTIVITIES*

In this work, influence of molecular weight and periodate modification ofβ-D-glucans isolated from Poria cocos sclerotium on the antitumor activities against Sar-coma 180 and Ehrlich ascites carcinoma (EAC) tumor was studied. The results show thattwo glucans PC3 (linear β-(1→3)-D-glucan) and PC4 [β-(1→3)-D-glucan with a fewof branches and glucuronic acid] are devoid of antitumor activity. However, when theglucans were modified by periodate oxidation, borohydride reduction and mild hydrolysisor partially hydrolysis, the derivatives have obvious antitumor activities. The decreasein molecular weight of glucans after periodate modification hardly affects their antitumoractions, but on the other hand, the decrease of molecular weight without periodate modi-fication could lead to an enhancement of the antitumor activities. Moreover, the glucansand these derivatives have much higher enhancement ratios of body weight of mice thanthat of 5-Fluorouracil (5-Fu), suggesting that they are less toxic than 5-Fu.     

Synthesis of Gibbilimbols A ～ D and Their ( Z )-Isomers

Gibbilimbols (1) were isolated from the leaves of Piper gibbilimbum in Papua New Guinea, which showed cyto toxicity toward KB nasopharyngal cancer cells (EDs0 2～ 8 μg/mL) and antibacterial activity against Staphylococcus epidermidis and Bacillus cereus (MIC 2 ～4 μg/mL). [1] Only two methods were reported for the synthesis of them,one is a coupling of phenolic part with alkyne, followed by reduction of triple bond by Mori. [2]     

BrΦnsted acid-promoted ‘on-water’ C(sp^3)-H functionalization fot the synthesis of isoindolinone/[1,2,4]triazolo[1,5-a]pyrimidine derivatives targeting the SKP2-CKS1 interaction

The isoindolinone and biaryl scaffolds are prevalent in natural products and drug molecules,which have showed broad and interesting biological activities.The efficient construction of such hybridized molecules and biological evaluation are of great interest to medicinal chemistry community.In this communication,we report an efficient BrΦnsted acid-promoted C(sp^3)-H functionalization approach that enables the rapid construction of biologically important isoindolinone/[1,2,4]triazolo[1,5-a]pyrimidine hybrids from 5-methyl-7-(2,4,6-trimethoxyphenyl)-[1,2,4]triazolo[1,5-a]pyrimidine,2-formylbenzoic acid and various anilines.The title compounds were generated in high to excellent yields(up to 96%)regardless of the electronic nature and steric effects of the substituents.In this reaction,an isoindolinone scaffold,one C-C single bond,and two C-N bonds were formed simultaneously with high atom economy.In this work,we have envisioned that the methyl group linked to the electron-deficient Nheterocycles could be used as a new synthetic handle for late-state diversification and may have broad applications in the field of organic and medicinal chemistry.Besides,the title compounds have exhibited promising activity against the SKP2-CKS1 interaction.     

The ionic parachor and predicting properties of amino acid ionic liquid homologues of 1-alkyl-3-methylimidazolium glycine

The amino acid ionic liquids(AAILs) [C3mim][Gly](1-propyl-3-methylimidazolium glycine) and [C4mim][Gly](1-butyl-3methylimidazolium glycine) have been prepared by the neutralization method and characterized by 1 H NMR spectroscopy and differential scanning calorimetry(DSC).The values of their density,surface tension and refractive index were measured at(298.15 ± 0.05) K.Since the AAILs can form strong hydrogen bonds with water,small amounts of water are difficult to remove from the AAILs by common methods.In order to eliminate the effect of the impurity water,the standard addition method(SAM) was applied to these measurements.A new concept which is called the ionic parachor has been put forward.The [C n mim] + cations were treated as a group of reference ions and the individual values of their ionic parachor were evaluated in terms of an extrathermodynamic assumption.Then,using the values of the ionic parachor of reference ions,the parachor,surface tension γ and refractive index n D of the ionic liquids investigated in this work were estimated.The estimated values correlate quite well with the corresponding experimental values.     

两种希夫碱对大肠杆菌抗菌活性的微量热法研究

The microcalorimetric method was used to study the antibacterial activity of two newly synthesized Schiff base compounds （H2L3＇ and H2L3） on Escherichia coli, trying to obtain the action on both of multiplying bacteria and non-multiplying bacteria at one experiment. The metabolic power-time curves of the bacteria treated with the compounds were obtained, and the thermokinetic parameters were analyzed, from which the antibacterial activities of these compounds were evaluated. The results showed that both of the two compounds have good activity on aerobic multiplying metabolism of E. coli, with the value of ICso 75.8 and 168.8 mg/L respectively, but have not effective action on fermentation metabolism of E. coli. The action of the compounds on the non-multiplying metabolism was investigated by taking the heat output of E. coli in the stationary phase as the guideline of the activity. The value of MSCso （minimum stationary-cidal concentration 50） of them is 118 and 187.5 mg/L, respectively. So, H2L^3 has stronger antibacterial action on E. coli than H2L^3 either for multiplying bacteria or non-multiplying bacteria, and their activity on the aerobic multiplying bacteria of E. coil is mainly shown. It does strongly suggest that the calorimetric method should play an important role in the fight against the drug-resistant bacteria.     

Synthesis,Crystal Structure and Antitumor Activity of Mixed Ligand Coordination Compound of Copper with Norfloxacin and 1,10-Phen,[Cu(NFLX)(phen)(H_2O)] NO_3·3H_2O

Fluoroquinolones are the widely used antibiotics for treating of numerous diseases1-4. Norfloxacin(1-ethyl-6-fluoro-4-oxo-7-(1-piperazinyl)-1,4dihydroquinoline-3-carboxylicacid, NFLX) is a typical member of this family and its metal coordination compounds have also received much more attention5-11. Apart from the synthesis and physicochemical properties of the coordination compounds, their antibacterial properties were also tested7-13, but there was scare report on antitumor properties of th…     

Synthesis and antitumor activities of structure-related small molecular compounds of gambogic acid

Through simplifying the complicated skeleton of the natural product gambogic acid, two series derivatives of chromone and xanthone were synthesized and examined for their antitumor activities against several cancer cells in vitro by MTT method. The results showed that appropriate introduction of prenyl group to the small molecular compounds could elevate their antitumor activities. The structure-activities relationship of synthesized compounds certified that the bridgecore in gambogic acid was very important for keeping its antitumor activities.     

A New Cerebroside, Asperiamide A, from Marine Fungus Asperillus sp.

Cerebrosides and ceramides[1] have been isolated from a number of marine organisms such as sea stars, sea anemones, gorgonians, sponges, tunicates, dinoflagellates, and green algae. Some cerebroside and ceramides exhibited cytotoxic, antitumor,[2,3] immunostimulatory,[4] antifungal,[5] and antiviral[6] activites. In the search for bioactive components,two water soluble constituents, asperiamide A and adenosine, were isolated from the marine fungus Asperillus sp. The current report describes the structural elucidation of a new compound, aspefiamide A (1) and a known one, adenosine (2).     

Synthesis, Characterization and Structure of the Dimmer Complex [Ni(TSSB)(phen)H_2O]·C_2H_5OH·0.5H_2O

1 INTRODUCTION Schiff base complexes containing sulfur and com- plexes of amino acid Schiff bases[1～5] have recently aroused increasing interest because of their antiviral, anticancer and antibacterial activities. Taurine, an amino acid containing sulfur, is indispensable to human beings and has important physiological func- tions. Recently, we have found that the Shiff base derived from taurine has manifold coordination modes[4～10]. Aromatic-ring stacking interaction is an important …     

NEW HETEROCYCLIC SYSTEM SYNTHESIS H THE REACTION OF 2,3-DIHYDRO-1,5-BENZOTHIAZEPINES WITH DICHLOROCARBENE

The reaction of two series of 2,3-dihydro-1,5-henzothiazepines Ⅰ with dichloro-carbene,gave azirino[2,1-d][1,5]benzothiazepines Ⅷ,azirino[2,1-e][1,6]benzothiazocines Ⅸ,pyrrolo[2,1-b][1,3]benzothiazoles Ⅹ,substituted-cyclopropanes Ⅺ and 2H-1,4-benzothiazin-2-onesⅫ.The structures of these products were confirmed by the analytical and spectral data.CompoundⅧ and Ⅸ are two new ring systems.     

An Efficient Synthesis of [1,2,4]Triazolo[3,2-d][1,5]benzoxazepin-2-thiones, a Kind of Novel Tricyclic O,N-Heterocycles

A series of novel tricyclic O,N-heterocycles, [1,2,4]triazolo[3,2-d][1,5]benzoxazepin-2-thiones 7 were achieved via acid-induced ring closure of the geminal arylazo isothiocyanate compounds 5 which were derived from substituted chroman-4-ones, followed by feasible ring expansion with simultaneous insertion of the nitrogen atom into the carbon skeleton. The X-ray crystal structure of 7d was also described.