Synthesis,characterization and antimicrobial activity of novel xanthene sulfonamide and carboxamide derivatives

Xanthene intermediates 4a and 4b were obtained from the reduction of nitro xanthene derivatives 3a and 3b which were synthesized via condensation of dimedone with m-nitrobenzaldehyde and p-nitrobenzaldehyde, respectively. Then xanthene sulfonamide 6a–n, and xanthene carboxamide derivatives 8a–h were synthesized by reaction of amino xanthene 4a, 4b with sulfonyl chlorides 5a–g and acyl chlorides 7a–d. Structures of the novel amino xanthene compounds and xanthene sulfonamide/carboxamide derivatives were established by their spectral data and elemental analyses. Furthermore, all the synthesized compounds were tested in vitro for their antimicrobial activity. The results were compared with reference standard antibiotics, erythromycin and nystatin. 6c, 6f, 6m and 8b Compounds were found to display most effective antimicrobial activity against a series of bacteria and fungi.     

Design and synthesis of a novel fluorescence probe for Zn based on the spirolactam ring-opening process of rhodamine derivatives

The spirolactam ring-opening process of rhodamine derivative is one of the most useful mechanisms for controlling fluorescence properties. However, the open/closed equilibrium reaction of rhodamine spirolactam has not been well characterized. Therefore, we examined the relationship between the spirolactam ring-opening process of rhodamine derivatives and the structure of the xanthene moiety. Based on the results of this investigation, we selected a candidate xanthene moiety for a Zn²⁺ sensor, and successfully developed a new fluorescence probe for Zn²⁺.     

Synthesis of Dihydroquinoline-Based Derivatives of Fluorescent Rhodamine Dyes for Nucleic Acid Analysis by a Real-Time Polymerase Chain Reaction

Russian Journal of Bioorganic Chemistry - An optimized synthesis scheme for the dihydroquinoline-based derivatives of xanthene fluorescent dye has been developed. For the first time, their use as...     

Photophysical analysis of class I major histocompatibility complex protein assembly using a xanthene-derivatized beta2-microglobulin

Spectral changes and a sixfold increase in the emission intensity were observed in the fluorescence of a single xanthene probe (Texas red) attached to beta2m-microglobulin (beta2m) upon assembly of beta2m into a ternary complex with mouse H-2Kd heavy chain and influenza nuclear protein peptide. Dissociation of the labeled beta2m from the ternary complex restored the probe's fluorescence and absorption spectra and reduced the emission intensity. Thus changes in xanthene probe fluorescence upon association/dissociation of the labeled beta2m molecule with/from the ternary complex provide a simple and convenient method for studying the assembly/dissociation mechanism of the class I major histocompatibility complex (MHC-I) encoded molecule. The photophysical changes in the probe can be accounted for by the oligomerization of free labeled beta2m molecules. The fluorescence at 610 nm is due to beta2m dimers, where the probes are significantly separated spatially so that their emission and excitation properties are close to those of xanthene monomers. Fluorescence around 630 nm is due to beta2m oligomers where xanthene probes interact. Minima in the steady-state excitation (550 nm) and emission (630 nm) anisotropy spectra correlate with the maxima of the high-order oligomer excitation and emission spectra, showing that their fluorescence is more depolarized. These photophysical features are explained by splitting of the first singlet excited state of interacting xanthene probes that can be modeled by exciton theory.     

Cytotoxic xanthene derivatives from Homalium paniculiflorum

Two new xanthene derivatives, homapanicones A (1) and B (2), along with 11 known compounds (3–13), were isolated from the stems of Homalium paniculiflorum. Among them, homapanicones A (1) and B (2) represent the first example of naturally occurring xanthene derivatives with an oxidized aromatic B unit, and the known compounds (3–13) were isolated from this plant for the first time. These structures were established on the basis of extensive spectroscopic methods. Compounds 1 and 2 were tested for their cytotoxicities on HL-60, SMMC-7721, A-549, MCF-7, and SW480 human tumor cell lines. Homapanicones A (1) and B (2) showed cytotoxicities against various human cancer cell lines in the range of IC₅₀ at 4.08–24.14 μM.     

Nucleoside analogues as highly potent and selective inhibitors of herpes simplex virus thymidine kinase.

A series of carboxamide derivatives of 5'-amino-2',5'-dideoxy-5-ethyluridine has been prepared as inhibitors of HSV-TK (herpes simplex virus thymidine kinase). The most potent compounds were derived from xanthene, thioxanthene and dihydroanthracene carboxylic acids. The lead compounds show subnanomolar IC(50) values against HSV TKs.     

Structure-activity relationships of xanthene carboxamides,novel CCR1 receptor antagonists

The structure-activity relationships of xanthene carboxamide derivatives on the CCR1 receptor binding affinity and the functional antagonist activity were described. Previously, we reported a quaternarized xanthen-9-carboxamide 1 as a potent human CCR1 receptor antagonist that was derived from a xanthen-9-carboxamide lead 2a. Further derivatization of 2a focusing on installing an additional substituent into the xanthene ring resulted in the identification of 2b-1 with IC(50) values of 1.8nM and 13nM in the binding assay using human CCR1 receptors transfected CHO cells and in the functional assay using U937 cells expressing human CCR1 receptors, respectively.     

Eco-friendly and efficient one-pot synthesis of alkyl- or aryl-14H-dibenzo[a,j]xanthenes in water

Alkyl- or aryl-14H-dibenzo[a,j]xanthene derivatives are synthesized efficiently by the reaction of beta-naphthol and aliphatic and aromatic aldehydes in the presence of KAl(SO4)2 x 12 H2O (alum) under aqueous condition at 100 degrees C. Different types of aromatic and aliphatic aldehydes are used in the reaction and in all cases the products synthesized successfully. Several solvents were examined for this reaction; however, in terms of reaction yield and time, water was found to be the optimum solvent.     

Synthesis of Unsymmetrical Polymethine Cyanine Fluorescent Dyes for Nucleic Acid Analysis by Real-Time PCR

The synthesis of unsymmetrical polymethine cyanine derivatives of f luorescent dyes is described, and their potential as a component of hybridization probes for the real-time PCR technique is first demonstrated.     

Microwave assisted synthesis of novel tetrazole/sulfonamide derivatives based on octahydroacridine,xanthene and chromene skeletons as inhibitors of the carbonic anhydrases isoforms I,II, IV and VII

The synthesis of novel tetrazole/sulfonamide derivatives based on octahydroacridine, xanthene and chromene scaffold by using microwave (MW) assisted techniques is reported in this study. These synthesized hybrid compounds were assayed for the inhibition of carbonic anhydrase (CA, EC 4.2.1.1). The inhibitory activities were determined against three cytosolic human isoforms (hCA I, II and VII) and one membrane-associated (hCA IV) isoform. Some of the newly synthesized sulfonamides showed micromolar to nanomolar inhibitory activity against these enzymes.     

Mechanism of asymmetric hydrogenation by rhodium complexes with unsymmetrical P-chirogenic bisphosphine ligands

Using a series of the rhodium complexes with (1S,2S)-1-(R(1))methylphosphino-2-(R(2))(R(3))phosphinoethane (R(1), R(2) and R(3) = 1-adamantyl, t-butyl, cyclohexyl, cyclopentyl, methyl; abbreviated as unsymmetrical BisP*), very high enantioselectivities were observed when the di- or tri- substituted and tetra-substituted dehydro-alpha-amino acid derivatives were used as the substrates. The main factor to give high enantioselectivity is the repulsive interaction between the functional groups of the substrate and the bulky substituents of the unsymmetrical BisP*. Since the unsymmetrical BisP* has two independent chiral phosphorous atoms in the vicinity of the active site, the higher enantioselectivity than those by the C2 symmetric BisP* complexes can be obtained. Moreover, the fine-tuning to obtain extremely high enantioselectivity may be possible by changing the combination of the substituents on the two phosphorous atoms of the unsymmetrical BisP*.     

Investigation of staining,polarization and fluorescence microscopic properties of myoepithelial cells

Summary During studies of early arteriosclerotic lesions fibers with the staining properties of myosins were observed in epithelial cells of various organs. To obtain a basis for further studies, staining, oolarization and fluorescence microscopic properties of classical myoepithelial cells and tonofibrils were investigated. The tannic acid-phosphomolybdic acid (TP)-Levanol Fast Cyanine 5RN stain for myosins and related proteins was applied to sections of tongue and skin. In other series various milling dyes, xanthene dyes and Thiazine Red R were substituted for Levanol Fast Cyanine 5RN.Myoepithelial cells of lingual and eccrine sweat glands showed the microscopic properties of smooth muscle cells; tonofibrils had little or no affinity for the dyes tested. The terminal bar-terminal web system of glandular epithelium and the fibrous layer in ducts of eccrine sweat glands resembled myosins and differed significantly from proteins of the epiderminkeratin group, e.g. tonofibrils. In preliminary studies the iodinated xanthene dyes Rose Bengal G, Erythrosin B and Y were found suitable for light, fluorescence and electron microscopic studies.     

Biosynthesis of 1,2-dihydrocarotenoids in Rhodopseudomonas viridis: Experiments with inhibitors

The effects of the inhibitors diphenylamine (DPA), 2-(4-chlorophenylthio) triethylammonium chloride (CPTA) and nicotine on the biosynthesis of 1,2-dihydrocarotenoids by Rhodopseudomonas viridis (Rhodospirillaceae) have been investigated. Small amounts of 1,2-dihydro derivatives of phytoene, phytofluene and ξ-carotene and its unsymmetrical isomer, and 1,2,1′,2′,-tetrahydro derivatives of neurosporene and lycopene were isolated from R. viridis grown in the presence of DPA, although there was virtually no quantitative effect on the levels of the normal main carotenoids, neurosporene and lycopene and their 1,2-dihydro derivatives. Nicotine also had little effect on the overall carotenoid composition, but the formation of 1,2-dihydrocarotenoids was inhibited to some extent by CPTA. The 1,2-dihydro end group may thus be introduced by a hydrogenation reaction similar to the more familiar C-1,2 hydration reaction characteristic of carotenoid biosynthesis in other photo synthetic bacteria.     

Synthesis and photophysical properties of new fluorinated benzo[c]xanthene dyes as intracellular pH indicators.

Two new fluorinated benzo[c]xanthene dyes were synthesized by reaction of fluorinated 1,6-dihydroxynaphthalenes with 2,4- (and 2,5)-dicarboxy-3'-dimethylamino-2'-hydroxybenzophenone. The two critical fluorinated 1,6-dihydroxynaphthalene intermediates were prepared via a regioselective route. The fluorinated benzo[c]xanthene dyes exhibit desired lower pK(a) values (6.4 and 7.2, respectively) than their parent compound (pK(a)=7.5) while the pH-dependent dual-emission characteristics are well retained. Their cell-permeable esters have been prepared for intracellular applications.     

Comparative study of inhibitory specificity of liver monoamine oxidase in frogs <Emphasis Type="Italic">Rana ridibunda</Emphasis> and <Emphasis Type="Italic">Rana temporaria</Emphasis>

A comparative enzymological investigation of inhibitory specificity of the liver monoamine oxidases (MAO) from the two frog species, lake frog Rana ridibunda and grass frog Rana temporaria, revealed certain interspecies similarities and distinctions of this enzyme. The anti-monoamine oxidase effect of five derivatives of acridine, three derivatives of phenothiazine and one derivative of xanthene (pyronine G) was comparatively analyzed. The tested six-membered tricyclic compounds were shown to exert an irreversible inhibitory effect on the enzyme from both biological sources, displaying the same substrate deamination specificity. Thus, the rate of interaction of acridine and phenothiazine derivatives with the MAO active center in both frog species was considerably higher when activity was determined using noradrenaline versus N-methylhistamine, while that of pyronine G—when activity was determined using N-methylhistamine versus noradrenaline. Interspecies quantitative differences were found in the inhibitory efficacy and degree of selectivity of the tested tricyclic compounds, indicative of the differences in catalytic properties of liver MAO at the interspecies level in the representatives of the genus Rana, family Ranidae. The data of substratespecific inhibitory analysis provide indirect evidence of the existence of two molecular MAO forms in the liver of the studied frog species.     

The Phototoxicity of Xanthene Derivatives Against Escherichia coli, Staphylococcus aureus, and Saccharomyces cerevisiae

We assessed the phototoxicity of a series of xanthene derivatives against E. coli, S. aureus, and S. cerevisiae, measured the physicochemical properties of the photosensitizers, and found the relationship between them. Without illumination, the dyes tested showed almost the same level of inherent toxicity to the same organism, which showed the inherent toxicity of dyes was primarily dependent on the structure of parent molecule. Upon illumination, the photosensitizers showed obvious phototoxicity to all organisms. The dyes showed stronger phototoxicity to Gram-positive bacteria. With the increasing number of halogen substituents, the singlet oxygen yields increased and the phototoxic activity increased too. There was no obvious correlation between relative lipophilicity and activity in the current study. Our results showed xanthenes had the potential to act as alternatives to conventional antimicrobial compounds and also could be used for the decontamination of microbially polluted waters.     

Photodynamic activity of dyes with different DNA binding properties I. free-radical induction in DNA.

The photosensitizing efficiencies of eight dyes have been compared; two acridines, two xanthene derivatives, one sulphur-containing dye and three chemotherapeutic agents. The analysed reaction was the photosensitized induction of free radicals in calf-thymus DNA at low temperature. The binding of these dyes to DNA was first measured. Both strong (process I) and weak (process II) binding, with different intensities, either alone or together, were observed as mode of fixation. Whatever the nature of their binding, all the dyes used revealed a photosensitizing power as inducers of peroxide radicals in DNA. Their relative efficiencies, expressed as a function of the amount of dye molecules bound to DNA, were found to be very different. Intercalation, however, appeared to favour the free-radical induction as the first strongly bound molecules were more efficient.     

Structural characterization and surface activity of hydrophobically functionalized extracted pectins

The technological properties of pectins are generally influenced by their chemical modification. Thus, amidated pectins are important derivatives with good emulsifying properties at low concentrations. The present article focuses on the comparative study of physicochemical properties of three modified pectin derivatives. Various amphiphilic derivatives in which pectin is associated with hydrophobic amines chains were prepared. The reaction was carried out in heterogeneous medium in methanol at 20 °C for 7 days and with 0.5 pectin/alkylamine mass ratio. The degrees of amidation (DA) of the derivatives were calculated based on the results of FTIR spectroscopy. The surface-active properties of the modified pectins were determined by surface tension (air/water) and interfacial tension (oil/water) measurements. The aminolysis of pectins appears to be an interesting way to produce pectin derivatives with new properties able to stabilize oil-in-water emulsions.     

AlCl3 induced (hetero)arylation of 2,3-dichloroquinoxaline: a one-pot synthesis of mono/disubstituted quinoxalines as potential antitubercular agents

A direct and single-step method has been developed for the synthesis of mono and 2,3-disubstituted quinoxalines by using a AlCl(3) induced (hetero)arylation of 2,3-dichloroquinoxaline. Both symmetrical and unsymmetrical 2,3-disubstituted quinoxalines can be prepared conveniently by using this method under appropriate reaction conditions. The reaction proceeds via C-C bond formation and can be utilized for the preparation of a variety of quinoxaline derivatives from readily available starting materials and reagents. The molecular structure of a representative compound was confirmed by single crystal X-ray diffraction study. Some of the compounds synthesized were tested for chorismate mutase inhibitory properties in vitro and one compound showed promising activity representing one of the few examples of chorismate mutase inhibition by a heteroarene based small molecule.