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A simple method was employed for the synthesis of dihydropyrano[3, 2-b]chromenedione derivatives (4a-o) in high yields by condensation of 5, 5-dimethylcyclohexane-1, 3-dione(1), different aromatic aldehydes (2a-o), and 5-hydroxy-2-(hydroxymethyl)-4H-pyran-4-one(3), using meglumine as a stable and reusable catalyst. Meglumine, an amino sugar, was employed as an environmentally benign catalyst, due to its splendid properties such as being inexpensive, recyclable, and biodegradable. The accomplished protocol employs low catalyst loading and easy work-up for the synthesis of 5-hydroxy-2-(hydroxymethyl)-4H-pyran-4-one derivatives. A great asset is that without any significant loss, the catalyst could be recovered and reused for extended synthetic steps. This offer huge advantage to overcome recyclability issues. Our synthesized compounds were analyzed by IR, 1H, 13C NMR, mass spectra and evaluated for their antioxidant properties by 1, 1-diphenyl-2-picryl hydrazyl radical (DPPH), hydrogen peroxide(H2O2), and nitric oxide (NO) scavenging methods. The correlation in exhibition of antioxidant activity was effective at all doses. The binding interactions and molecular docking studies for entitled compounds were studied against 3MNG protein; 4k exhibited marked binding affinity with excellent docking score of −7.6 Kcal/mol and emerged as a lead compound. © 2019 Wiley Periodicals, Inc. Ural Federal University, UrFU The authors G. Sravya and N. Bakthavatchala Reddy are thankful to Ural Federal University, Yekaterinburg, Russia, for postdoctoral fellowship.

Acute lung injury remains a challenging clinical condition, necessitating the development of novel, safe and efficient treatments. The prevention of macrophage M1-polarization is a viable venue to tackle excessive inflammation. We performed a phenotypic screening campaign to identify azolopyrimidine compounds that effectively inhibit LPS-induced NO synthesis and interleukin 6 (IL-6) secretion. We identified lead compound 9g that inhibits IL-6 secretion with IC50 of 3.72 µM without apparent cytotoxicity and with minimal suppression of macrophage phagocytosis in contrast to dexamethasone. In a mouse model of LPS-induced acute lung injury, 30 mg/kg i.p. 9g ameliorated anxiety-like behavior, inhibited IL-6 release, and limited neutrophil infiltration and pulmonary edema. A histological study confirmed the protective activity of 9g. Treatment with compound 9g prevented the migration of CD68+ macrophages and the incidence of hemorrhage. Hence, we have identified a promising pharmacological approach for the treatment of acute lung injury that may hold promise for the development of novel drugs against cytokine-mediated complications of bacterial and viral infections. © 2022 by the authors. Licensee MDPI, Basel, Switzerland. Ministry of Education and Science of the Russian Federation, Minobrnauka: 075-15-2020-777 Funding: This research was funded by the Ministry of Science and Higher Education of the Russian Federation (Agreement on the provision of grants from the federal budget in the form of subsidies under paragraph 4 of Article 78.1 of the Budget Code of the Russian Federation, Moscow, 1 October 2020 No. 075-15-2020-777).

WOS: 000424646600026, In this study we report that amino acridine intermediates 7 and 8 were obtained from the reduction of nitro acridine derivatives 5 and 6 that were synthesized via the condensation of dimedone, p-nitrobenzaldehyde with various amine derivatives, respectively. Then acridine sulfonamide hybrid compounds (9-18) were synthesized by the reaction of amino acridine 7, 8 with sulfonyl chlorides. The new hybrid compounds were characterized by FT-IR, H-1-NMR, C-13-NMR, and HRMS analyzes. The evaluation of in vitro anticholinesterase action of the synthesized compounds against AChE showed that some of them are potent inhibitors. Among them, compound 17 showed the most potent activity against AChE with an IC50 of 0.14 A mu M.

A series of 1-(2,3-dihydro-1H-indan-1-yl)-3-aryl urea/thiourea derivatives (4a-j) have been synthesized from the reaction of 2,3-dihydro-1H-inden-1-amine (2) with various aryl isocyanates/isothiocyanates (3a-j) by using N,N-DIPEA base (Hunig's base) catalyst in THF at reflux conditions. All of them are structurally confirmed by spectral (IR, 1H & 13C NMR and MASS) and elemental analysis and screened for their in-vitro antioxidant activity against DPPH and NO free radicals and found that compounds 4b, 4i, 4h & 4g are potential antioxidants. The obtained in vitro results were compared with the molecular docking, ADMET, QSAR and bioactivity study results performed for them and identified that the recorded in silico binding affinities were observed in good correlation with the in vitro antioxidant results. The Molecular docking analysis had unveiled the strong hydrogen bonding interactions of synthesized ligands with ARG 160 residue of protein tyrosine kinase (2HCK) enzyme and plays an effective role in its inhibition. Toxicology studies have assessed the potential risks of 4a-j and inferred that all of them were in the limits of potential drugs. The conformational analysis of 4a-j inferred that the urea/thiourea spacer linking 2,3-dihydro-1H-inden-1-amino and substituted aryl units has facilitated all these molecules to effectively bind with ARG 160 amino acid residue present on the α-helix of the protein tyrosine kinase (2HCK) enzyme specifically on chain A of hemopoetic cell kinase. Collectively this study has established a relationship between the antioxidant potentiality and ligands binding with ARG 160 amino acid residue of chain A of 2HCK enzyme to inhibit its growth as well as proliferation of reactive oxygen species in vivo. © 2019 Elsevier Inc. One of the authors Dr. Avula Vijay Kumar Reddy is thankful to Ural Federal University, Yekaterinburg, Russian Federation for providing Postdoctoral Fellowship.

In this study, seven new 3(2H)-pyridazinone derivatives expected to show cytotoxic activity in liver and colon cancer cell lines were synthesized. Their structures were confirmed by the IR, 1 H-NMR, 13 C-NMR spectra and elementary analyses. Compunds V 1 -V 7 were tested on HEP3B (liver cancer) and HTC116 (colon cancer) cell lines for cytotoxicity by using MTS [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)- 2H-tetrazolium] proliferation assay. Human fibroblast cells were used as safety control in these tests. 6-[4-(2-Fluorophenyl)piperazine-1-yl]-3(2H)-pyridazinone-2-acetyl-2-(2-chlorobenzal)hydrazone (compound V 3 ) was the most active agent with respect to HEP3B and HTC116 cell lines. © 2019, Springer Science+Business Media, LLC, part of Springer Nature.

We describe the hitherto unknown use of N-Boc-protected hydrazine in the Ugi tetrazole reaction to access a library of highly substituted 5-(hydrazinomethyl)-1-methyl-1H-tetrazoles. The reaction is very versatile and good to high yielding. A one-pot, two-step procedure is given.

Innovative therapeutic heterocycles having precisely thiadiazolyl-pyranopyrazole fragments were prepared by using the ecofriendly synthetic route. Entire compounds formed in quantitative yields. All the composites tested for their antimicrobial effectiveness against four microbial, two beneficial fungi's and accurately measured the minimum inhibitory concentrations (MIC and MBC/MFC), along with some initial structure activity relationships (SARs) also discussed. From the biological outcomes, the motif 6f provided an outstanding activity against all six pathogens. The possible presence of a nitro substituent on this composite may undoubtedly enhance the activity. In addition, amalgams 6d, 6g and 6l displayed promising antimicrobial results. This may be justified to the presence of electron capture group attached to the benzene ring, while the combinations 6j and 6k were zero effect towards all bacterial strains. The other compounds were excellent to low antimicrobial efficiency. The intriguing point was observed that all the active compounds had in common immense antibacterial effectiveness on Gram-negative bacteria than Gram-positive one and more antifungal activity on A. niger compare to other fungus. All things considered and suggested that this outstanding green synthetic approach is used to develop biological active compounds. On top of that, biological results confirmed that these biologically energetic motifs suitable for additional preclinical examine with the aim of standing novel innovative drugs. © 2018 Elsevier Inc.

PubMed ID: 31247220 As seen in other types of cancer, development of drug resistance in NSCLC treatment causes adverse effects on disease fighting process. Recent studies have shown that one of the drug resistance development mechanisms is that cancer cells may acquire the ability to escape from cell death. Therefore, development of anticancer drugs which have the strategy to redirect cancer cells to any cell death pathways may provide positive results for cancer treatments. Autophagy may be a target mechanism of alternative cancer treatment strategy in cases of blocked apoptosis. There is also a complex molecular link between autophagy and apoptosis, has not been fully understood yet. The dicyano compound which we used in our study caused cell death in NSCLC cell lines. When we analyzed the cells which were treated with dicyano compound by transmission electron microscope, we observed autophagosome structures. Upon this result, we investigated expression levels of autophagic proteins in the dicyano compound-treated cells by immunoblotting and observed that expression levels of autophagic proteins were increased significantly. The TUNEL assay and qRT-PCR for pro-apoptotic and anti-apoptotic gene expression, which we performed to assess apoptosis in the dicyano compound-treated cells, showed that the cell death does not occur through apoptotic pathway. We showed that the dicyano compound, which was developed in our laboratories, may play a role in molecular link between apoptosis and autophagy and may shed light on development of new anticancer treatment strategies. © 2019 Elsevier B.V. 2017SAE024 We are grateful to Dr. Nedim KARAGENC because of his valuable contributions. This study was supported by Pamukkale University Research Foundation ( 2017SAE024 ).

WOS: 000485335600003, Novel 3-Amino-1-hetarylfluorene derivatives have medicinal uses and challenging transformation in organic synthesis have been synthesized via decyanation process. Surprisingly, the alkylated compounds derived from 3-Amino-1-hetarylfluorenes were obtained via further nucleophilic substitution to the 9-C and 3-N positions of the fluorene ring because of the harsh reaction condition employed. The synthesized compounds were characterized by spectroscopic techniques as well as X-ray single crystal diffraction analysis. This new family of blue emitting fluorene derivatives have low to moderate quantum yields (the largest value of Phi(F) = 0.52 for compound 15). (C) 2019 Elsevier Ltd. All rights reserved., Scientific and Technological Research Council of Turkey (TUBITAK)Turkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [113Z704], This research was supported by The Scientific and Technological Research Council of Turkey (TUBITAK) Grant no: 113Z704.

Basic bulky amines such as amantadine are well-characterized M2 channel blockers, useful for treating influenza. Herein we report our surprising findings that charge-neutral, bulky isocyanides exhibit activities similar to - or even higher than - that of amantadine. We also demonstrate that these isocyanides have potent growth inhibitory activity against the H5N1 virus. The -NH2 to -N?C group replacement within current anti-influenza drugs was found to give compounds with high activities at low-micromolar concentrations. For example, a tenfold improvement in potency was observed for 1-isocyanoadamantane (27), with an EC50 value of 0.487 ?m against amantadine-sensitive H5N1 virus as determined by both MTT and plaque-reduction assays, without showing cytotoxicity. Furthermore, the isocyanide analogues synthesized in this study did not inhibit the V27A or S31N mutant M2 ion channels, according to electrophysiology experiments, and did not exhibit activity against amantadine-resistant virus strains. Charge-neutral bulky isocyanides were found to exhibit antiviral activities similar to - or even higher than - that of amantadine. Moreover, we demonstrated that these isocyanides have potent growth inhibitory activity against the wild-type H5N1 virus. The NH2 to N?C group replacement within current anti-influenza drugs was found to result in compounds with low-micromolar activities. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

A facile one-pot synthesis of mono(hpp)- or di(hpp)-substituted N-heterocyclic ligands from halogenated N-heterocycles and 1,3,4,6,7,8-hexahydro-2H-pyrimido[1,2-a]pyrimidine (H-hpp) is presented. N,N-Bidentate and N,N,N-tridentate ligands incorporating electron-donating and electron-withdrawing substituents can also be readily synthesized using this method. � Georg Thieme Verlag Stuttgart, New York.

Cereal-associated Lactic Acid Bacteria (LAB) are well known for homopolymeric exopolysaccharide (EPS) production. Herein, the structure of an EPS isolated from sourdough isolate Lactobacillus brevis E25 was determined. A modified BHI medium was used for production of EPS-E25 in order to eliminate potential contaminants. Analysis of sugar monomers in EPS revealed that glucose was the only sugar present. Structural characterisation of EPS by NMR and methylation analysis revealed that E25 produced a highly branched ?-glucan with (?1 ? 3) and (?1 ? 6) glycosidic linkages, and was similar in structure to a previously reported EPS from Lactobacillus reuteri 180. The 1H and 13C NMR data were contrasted with newly recorded data for known polysaccharides (alternan, commercial dextran) which also contain ?-(1,3,6)Glc branch points. It was found in both E25 EPS and alternan that NMR parameters could be used to distinguish glucose residues that had the same substitution pattern but occupied different positions in the structure. © 2017 Elsevier Ltd

Apocarotenoids are widely distributed among living organisms (bacteria, fungi, algae, plants and even animals) and have been associated with several signaling functions. These compounds are generated by the activity of carotenoid cleavage dioxygenases (CCDs), whose diversity greatly contributes to the large number of apocarotenoids that have been described so far. It is nevertheless expected that a considerable diversity of these molecules is yet to be discovered. In this work, we describe the isolation and structural elucidation of the apocarotenoid 4-oxo-β-apo-13-carotenone from the cultured freshwater cyanobacterium Anabaena cylindrica PCC 7122, corresponding to the first report of this compound from natural sources. © 2018 Wiley-VHCA AG, Zurich, Switzerland We thank CEMUP for NMR and MS analyses. This work was supported by R&D&I INNOVMAR - Innovation and Sustainability in the Management and Exploitation of Marine Resources (reference NORTE-01-0145-FEDER-000035, Research Line NOVELMAR), funded by the Northern Regional Operational Program (NORTE2020) through the European Regional Development Fund (ERDF), and by Funda©cão para a Ciência e a Tecnolo-gia, through grant IF/01358/2014 to PNL.

Candida spp. is associated with almost 80% of all nosocomial fungal infections and is considered a major cause of blood stream infections. In humans, Cryptococcosis is a disease of the lungs caused by the fungi Cryptococcus gattii and Cryptococcus neoformans. It can be potentially fatal, especially in immune-compromised patients. In a search for antifungal drugs, Deguelia duckeana extracts were assayed against these two fungi and also against Candida albicans, which causes candidiasis. Hexane branches and CH2Cl2 root extracts as well as the substances 4-hydroxylonchocarpine, 3,5,4′-trimethoxy-4-prenylstilbene and 3′,4′-methylenedioxy-7-methoxyflavone were assayed to determine the minimal inhibitory concentration. Phytochemical study of CH2Cl2 root and hexane branch extracts from D. duckeana A.M.G. Azevedo, Fabaceae, resulted in the isolation and characterization of nine phenolic compounds: 4-hydroxyderricine, 4-hydroxylonchocarpine, 3′,4′,7-trimethoxy-flavonol, 5,4′-dihydroxy-isolonchocarpine, 4-hydroxyderricidine, derricidine, 3,5,4′-trimethoxy-stilbene, 3′,4′,7-trimethoxyflavone and yangambin. The only active extract was a CH2Cl2 root showing minimal inhibitory concentration 800 μg/ml against C. gattii, and the investigation of compounds obtained from this extract showed that 4-hydroxylonchocarpine was active against all three fungi (C. neoformans, C. gattii and C. albicans). These results suggest that D. duckeana extracts have potential therapeutic value for the treatment of pathogenic fungi. Keywords: Amazonian plant, Chalcone, Flavonoid, Lignan, Stilbene, Timbó

The synthesis of 3-amino-1,2,4-triazole via mercury(II) chloride-mediated cyclization of amidinothiourea is described. This procedure offers a general and efficient route to synthesize the title compound by 3 + 2 annulation reaction. On the basis of the literature precedence, the mechanism for the formation of 3-amino-1,2,4-triazole is proposed. When the synthesized compounds were tested for their antimicrobial activity showed promising inhibition against tested microbes.

The synthesis of 3-amino-1,2,4-triazole via mercury(II) chloride-mediated cyclization of amidinothiourea is described. This procedure offers a general and efficient route to synthesize the title compound by 3 + 2 annulation reaction. On the basis of the literature precedence, the mechanism for the formation of 3-amino-1,2,4-triazole is proposed. When the synthesized compounds were tested for their antimicrobial activity showed promising inhibition against tested microbes.

A series of novel naphthoquinone amide derivatives of the bioactive quinones, plumbagin, juglone, menadione and lawsone, with various amino acids were synthesized. The compounds were characterized by 1H NMR, 13C NMR, Mass, IR and elemental analysis. All the compounds were evaluated for their anticancer activity against HeLa and SAS cancer cell lines and 3D-QSAR indicated the presence of electron donating group near sulphur enhanced the activity against HeLa cells. Among the derivatives synthesized, compounds 11f, 10a, 10b and 10g were the most active with IC50 values of 16, 12, 14 and 24.5 ?M, respectively. The analogues were also screened for antimicrobial activity against two human bacterial pathogens, the Gram-positive Methicillin resistant Staphylococcus aureus (MRSA) and the Gram-negative Pseudomonas aeruginosa and a human yeast pathogen, Fluconazole resistant Candida albicans (FRCA). Among the synthesized compounds, 8g, 10g and 11g exhibited maximum antibacterial activity towards MRSA and antifungal activity against FRCA in well diffusion method. � 2014 Elsevier Ltd. All rights reserved.

Tryptamine- and phenethylamine-derived imides were selectively monotrifluoromethylated using CF3TMS. Subsequent methanesulfonic acid mediated cyclization of the intermediate hemiaminals afforded the ?-trifluoromethylated amine derivatives via the formation of trifluoromethylated acyliminium ions, in one pot. The strategy was applicable to the both inter- and intramolecular versions. Furthermore, the utility of the present method was demonstrated through the synthesis of trifluoromethylated analogues of harmicine and crispine A. � 2014 American Chemical Society.

Saponins are amphiphilic glycoconjugates which give soap-like foams in H2O. A new triterpenoid saponin, simenoside A (1), based on gypsogenin aglycone, and the known saponin 2 were isolated from Gypsophila simonii Hub.-Mor. The structure of the new saponin was elucidated as 3-O-ß-D-galactopyranosyl-(1›2)-[ß-D-xylopyranosyl-(1›3)] -ß-D-glucuronopyranosylgypsogenin 28-O-ß-D-glucopyranosyl-(1›3)- [ß-D-glucopyranosyl-(1›2)-ß-D-xylopyranosyl-(1›4)] -?-L-rhamnopyranosyl-(1›2)-ß-D-fucopyranosyl ester on the basis of extensive spectral analyses and chemical evidence. Saponins 1 and 2 were isolated from G. simonii for the first time. Copyright © 2014 Verlag Helvetica Chimica Acta AG, Zürich.

The acylation of arylhydrazonoethanethioamides containing primary amino group did not yield acylthioamides as expected. Surprisingly, the cyclic 5-acylimino-2,5-dihydro-1,2,3-thiadiazoles were obtained. The formation of thiadiazoles in this reaction was explained by the higher ability of arylhydrazono-N-acylthioacetamide intermediates to be oxidized comparing to their precursors. The presence of pseudobicyclic aromatic structure in the reaction product was a main factor favoring the formation of 1,2,3-thiadiazole ring. © 2013 Elsevier Ltd. All rights reserved.

While 1,3-dicarbonyl compounds react with (E)-1,1,1-trifluoro-3-nitrobut-2- ene in the presence of sodium acetate to produce the target β- (trifluoromethyl)furans, their reaction with (E)-1,1,1-trichloro-3-nitrobut-2- ene, under the same conditions, took an entirely different course and gave spiro-gem-dichlorocyclopropanes bearing a 1-nitroethyl moiety, with high diastereoselectivity and in good yields. © 2013 Elsevier Ltd. All rights reserved.

A new class of highly stable O,N,N,O-tetradentate bioxazoline ligands were synthesized from l-tartaric acid. Exploration of those ligands in Pd-catalyzed asymmetric allylic alkylation yielded alkylated product up to 96% ee. Necessity of additional chelation to obtain high enantioselectivity was also demonstrated. Structural modifications of this ligand might result in identification of a novel privileged chiral ligand from an inexpensive chiral pool. � 2013 Elsevier Ltd. All rights reserved.

1,3-Bis(2-pyridylimino)isoindoline derivative bearing 3,4-ethylenedioxythiophene ( EDOT-BPI ) and its palladium complex ( EDOT-PdBPI ) were synthesized and characterized by FT-IR, 1 H NMR, 13 C NMR, UV–Vis spectroscopies and via mass spectrometric analysis. Polymerization of EDOT-PdBPI and copolymerization with 4-amino-N-(2,5-di(thiophene-2-yl)-1 H -pyrrol-1-yl)benzamide ( HKCN ) were carried out by an electrochemical method. In addition, P(EDOT-PdBPI- co -HKCN) modified graphite rod electrode was improved for amperometric glucose sensor based on glucose oxidase (GOx). In this novel biosensor matrix, amino groups in HKCN were used for the enzyme immobilization. On the other hand, EDOT-PdBPI used to mediate the bioelectrocatalytic reaction. Amperometric detection was carried out following oxygen consumption at −0.7 V vs. the Ag reference electrode in phosphate buffer (50 mM, pH 6.0). The novel biosensor showed a linear amperometric response for glucose within a concentration range of 0.25 mM to 2.5 mM (LOD: 0.176 mM). Amperometric signals at 1 mM of glucose were 17.9 μA under anaerobic conditions. Amperometric response of the P(EDOT-PdBPI- co -HKCN)/GOx electrode decreased only by 13% within eight weeks. The P(EDOT-PdBPI- co -HKCN)/GOx electrode showed good selectivity in the presence of ethanol and phenol. This result shows that, modification of the proposed biosensor by copolymerization of amine functionalized monomer, which is indispensable to the enzyme immobilization, with palladium complex bearing monomer, which is mediate the bioelectrocatalytic reaction, have provided to give perfect response to different glucose concentrations.

Chiral secondary alcohols are convenient mediator for the synthesis of biologically active compounds and natural products. In this study fifteen yeast strains belonging to three food originated yeast species Debaryomyces hansenii, Saccharomyces cerevisiae and Hanseniaspora guilliermondii were tested for their capability for the asymmetric reduction of acetophenone to 1-phenylethanol as biocatalyst microorganisms. Of these strains, Debaryomyces hansenii P1 strain showed an effective asymmetric reduction ability. Under optimized conditions, substituted acetophenones were converted to the corresponding optically active secondary alcohols in up to 99% enantiomeric excess and at high conversion rates. This is the first report on the enantioselective reduction of acetophenone by D. hansenii P1 from pastırma, a fermented Turkish meat product. The preparative scale asymmetric bio reduction of 3-methoxy acetophenone 1g by D. hansenii P1 gave (R)-1-(3-methoxyphenyl) ethanol 2g 82% yield, and >99% enantiomeric excess. Compound 2g can be used for the synthesis of (+)-NPS-R-568 [3-(2-chlorophenyl)-N-[(1R)-1-(3-methoxyphenly) ethyl] propan-1-amine] which have a great potential for the treatment of primary and secondary hyper-parathyroidism. In addition, D. hansenii P1 successfully reduced acetophenone derivatives. This study showed that this yeast can be used industrially to produce enantiomerically pure chiral secondary alcohols, which can be easily converted to different functional groups.

Highly important trans-3,4-dihydro-2H-1,4-benzoxazine moieties were easily synthesized by domino aziridine ring opening with o-bromophenols and o-chlorophenols followed by the palladium catalyzed coupling-cyclization (intramolecular C (aryl)-N (amide) bond formation) with good to excellent yields. � 2012 Elsevier Ltd. All rights reserved.

The Escherichia coli Metabolome Database (ECMDB, http://www.ecmdb.ca) is a comprehensively annotated metabolomic database containing detailed information about the metabolome of E. coli (K-12). Modelled closely on the Human and Yeast Metabolome Databases, the ECMDB contains >2600 metabolites with links to ∼1500 different genes and proteins, including enzymes and transporters. The information in the ECMDB has been collected from dozens of textbooks, journal articles and electronic databases. Each metabolite entry in the ECMDB contains an average of 75 separate data fields, including comprehensive compound descriptions, names and synonyms, chemical taxonomy, compound structural and physicochemical data, bacterial growth conditions and substrates, reactions, pathway information, enzyme data, gene/protein sequence data and numerous hyperlinks to images, references and other public databases. The ECMDB also includes an extensive collection of intracellular metabolite concentration data compiled from our own work as well as other published metabolomic studies. This information is further supplemented with thousands of fully assigned reference nuclear magnetic resonance and mass spectrometry spectra obtained from pure E. coli metabolites that we (and others) have collected. Extensive searching, relational querying and data browsing tools are also provided that support text, chemical structure, spectral, molecular weight and gene/protein sequence queries. Because of E. coli's importance as a model organism for biologists and as a biofactory for industry, we believe this kind of database could have considerable appeal not only to metabolomics researchers but also to molecular biologists, systems biologists and individuals in the biotechnology industry. © The Author(s) 2012.

Poly-N-acetyllactosamine extensions on N-and O-linked glycans are increasingly recognized as biologically important structural features, but access to these structures has not been widely available. Here, we report a detailed substrate specificity and catalytic efficiency of the bacterial β3-N-acetylglucosaminyltransferase (β3GlcNAcT) from Helicobacter pylori that can be adapted to the synthesis of a rich diversity of glycans with poly-LacNAc extensions. This glycosyltransferase has surprisingly broad acceptor specificity toward type-1,-2,-3 and-4 galactoside motifs on both linear and branched glycans, found commonly on N-linked, O-linked and I-antigen glycans. This finding enables the production of complex ligands for glycan-binding studies. Although the enzyme shows preferential activity for type 2 (Galβ1-4GlcNAc) acceptors, it is capable of transferring N-acetylglucosamine (GlcNAc) in β1-3 linkage to type-1 (Galβ1-3GlcNAc) or type-3/4 (Gal1-3GalNAc/) sequences. Thus, by alternating the use of the H. pylori β3GlcNAcT with galactosyltransferases that make the 1-4 or 1-3 linkages, various N-linked, O-linked and I-antigen acceptors could be elongated with type-2 and type-1 LacNAc repeats. Finally, one-pot incubation of di-LacNAc biantennary N-glycopeptide with the β3GlcNAcT and GalT-1 in the presence of uridine diphosphate (UDP)-GlcNAc and UDP-Gal, yielded products with 15 additional LacNAc units on the precursor, which was seen as a series of sequential ion peaks representing alternative additions of GlcNAc and Gal residues, on matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) analysis. Overall, our data demonstrate a broader substrate specificity for the H. pylori β3GlcNAcT than previously recognized and demonstrate its ability as a potent resource for preparative chemo-enzymatic synthesis of complex glycans. © 2012 The Author.

Pasteurella multocida strains are classified using the Heddleston lipopolysaccharide (LPS) serotyping scheme into 16 serovars. Understanding the structural and genetic basis for this LPS typing scheme is important because protection against infections caused by P. multocida is generally considered to be serovar specific. Here we show that the serovar 14 type strain P2225 and the serovar 1 strains X73 and VP161 express similar LPS structures. However, the serovar 14 LPS lacks the terminal phosphocholine (PCho) residues present on the serovar 1 LPS and contains the 1,4-linked β-galactose but not the 1,6-linked β-galactose. Sequencing analysis of the LPS biosynthesis outer core loci of P2225 and the serovar 1 type strain X73 showed that they were nearly identical. However, the phosphocholine biosynthesis gene, pcgA of P2225 contained a 19 bp nucleotide deletion. Complementation of P2225 with an intact pcgA resulted in an LPS structure identical to that expressed by serovar 1 strain VP161 and highly similar to that expressed by strain X73, with a 1,6-linked β-galactose and both terminal PCho residues. This study has shown unequivocally that strains belonging to serovar 1 and 14 share a common LPS outer core locus and that minor changes within this locus can dramatically alter the LPS structure expressed on the surface of P. multocida , and thus has implications into our understanding of the potential to generate cross-protective vaccines.

A small library of diversely substituted 2,4,6,8-tetraaryl-3,7- diazabicyco[3.3.1]nonan-9-ones, their oximes and O-methyloximes were achieved in a stereocontrolled manner by an easiest synthetic strategy as single isomers with high yields. Stereochemistry of all the synthesized compounds was established by their 1D/2D NMR spectral studies, further, witnessed by single-crystal XRD analysis. Accordingly, the compounds exist in a chair-boat conformation with equatorial orientation of the substituents in the chair part and boat-axial orientation in the boat part. Finally, all the synthesized oximes and oxime ethers were evaluated for their in vitro antimicrobial activity against a panel of pathogenic bacteria and fungi, and as a result of the structure-activity correlations, some lead molecules were known for further optimization. � 2010 Elsevier Ltd. All rights reserved.

Membrane proteins pose problems for the application of NMR-based ligand-screening methods because of the need to maintain the proteins in a membrane mimetic environment such as detergent micelles: they add to the molecular weight of the protein, increase the viscosity of the solution, interact with ligands non-specifically, overlap with protein signals, modulate protein dynamics and conformational exchange and compromise sensitivity by adding highly intense background signals. In this article, we discuss the special considerations arising from these problems when conducting NMR-based ligand-binding studies with membrane proteins. While the use of13C and15N isotopes is becoming increasingly feasible,19F and1H NMR-based approaches are currently the most widely explored. By using suitable NMR parameter selection schemes independent of or exploiting the presence of detergent,1H-based approaches require least effort in sample preparation because of the high sensitivity and natural abundance of1H in both, ligand and protein. On the other hand, the19F nucleus provides an ideal NMR probe because of its similarly high sensitivity to that of1H and the lack of natural19F background in biologic systems. Despite its potential, the use of NMR spectroscopy is highly underdeveloped in the area of drug discovery for membrane proteins. © 2010 John Wiley & Sons A/S.

Membrane proteins pose problems for the application of NMR-based ligand-screening methods because of the need to maintain the proteins in a membrane mimetic environment such as detergent micelles: they add to the molecular weight of the protein, increase the viscosity of the solution, interact with ligands non-specifically, overlap with protein signals, modulate protein dynamics and conformational exchange and compromise sensitivity by adding highly intense background signals. In this article, we discuss the special considerations arising from these problems when conducting NMR-based ligand-binding studies with membrane proteins. While the use of13C and15N isotopes is becoming increasingly feasible,19F and1H NMR-based approaches are currently the most widely explored. By using suitable NMR parameter selection schemes independent of or exploiting the presence of detergent,1H-based approaches require least effort in sample preparation because of the high sensitivity and natural abundance of1H in both, ligand and protein. On the other hand, the19F nucleus provides an ideal NMR probe because of its similarly high sensitivity to that of1H and the lack of natural19F background in biologic systems. Despite its potential, the use of NMR spectroscopy is highly underdeveloped in the area of drug discovery for membrane proteins. © 2010 John Wiley & Sons A/S.

The cycloaddition reaction of azomethine ylides, generated through decarboxylation, with (E)-3-arylidene-4-chromanones as dipolarophiles has been investigated. A high degree of regioselectivity has been observed in the synthesis of a new class of functionalized dispiroheterocyclic compounds bearing chromanone and acenaphthenequinone framework. The structures were established by spectroscopic techniques as well as single crystal X-ray analysis. � 2009 Elsevier Ltd. All rights reserved.

Submitted by Vitor Silverio Rodrigues (vitorsrodrigues@reitoria.unesp.br) on 2014-05-27T11:23:41Z No. of bitstreams: 0Bitstream added on 2014-05-27T14:33:59Z : No. of bitstreams: 1 2-s2.0-59649108290.pdf: 169403 bytes, checksum: adbc0484760cc3afa3fd9d671eaad3b6 (MD5) Made available in DSpace on 2014-05-27T11:23:41Z (GMT). No. of bitstreams: 0 Previous issue date: 2008-10-01 Schistosomiasis, an important disease in Brazil, is caused by a trematode of the genus Schistosoma, reaching millions of person in one of the most endemic region of this disease in the whole globe. The main goal of this work was to syntetize the 6-formyl- oxamniquine derivative and evaluate its biological activity. The 6-formyl-oxamniquine derivative was obtained by the oxidation of oxamniquine with MnO 2, applying CH 2Cl 2 as solvent at room temperature for 24 hours. The obtaintion of 6-formyl-oxamniquine derivative compound was confirmed by IR spectroscopy and 13C NMR and 1H NMR, presenting similar activity when compared to the commercial oxamniquine (Mansil®). Laboratório de Pesquisa e Desenvolvimento de Fármacos Departamento de Fármacos e Medicamentos Universidade Estadual Paulista Júlio de Mesquita Filho Departamento de Fármacos e Medicamentos Faculdade Faculdade de Ciências Farmacêuticas Universidade Estadual Paulista Júlio de Mesquita Filho Laboratório de Helmintologia Departamento de Parasitologia Universidade Estadual de Campinas Laboratório de Parasitologia Departamento de Ciências Biológicas Universidade Estadual Paulista Júlio de Mesquita Filho Departamento de Química Orgânica Universidade Federal de São Carlos Faculdade de Ciências Farmacêuticas UNESP, Rod. Araraquara-Jaú, km. 01, 14801-902 - Araraquara - SP Laboratório de Pesquisa e Desenvolvimento de Fármacos Departamento de Fármacos e Medicamentos Universidade Estadual Paulista Júlio de Mesquita Filho Departamento de Fármacos e Medicamentos Faculdade Faculdade de Ciências Farmacêuticas Universidade Estadual Paulista Júlio de Mesquita Filho Laboratório de Parasitologia Departamento de Ciências Biológicas Universidade Estadual Paulista Júlio de Mesquita Filho Faculdade de Ciências Farmacêuticas UNESP, Rod. Araraquara-Jaú, km. 01, 14801-902 - Araraquara - SP

The structure of the SodCII-encoded monomeric Cu, Zn superoxide dismutase from Salmonella enterica has been solved by NMR spectroscopy. This represents the first solution structure of a natural and fully active monomeric superoxide dismutase in solution, providing information useful for the interpretation of the evolutional development of these enzymes. The protein scaffold consists of the characteristic beta-barrel common to the whole enzyme family. The general shape of the protein is quite similar to that of Escherichia coli Cu, Zn superoxide dismutase, although some differences are observed mainly in the active site. SodCII presents a more rigid conformation with respect to the engineered monomeric mutants of the human Cu, Zn superoxide dismutase, even though significant disorder is still present in the loops shaping the active site. The analysis of both dynamics and hydration properties of the protein in solution highlights the factors required to maintain the fully active and, at the same time, monomeric protein. This study provides novel insights into the functional differences between monomeric and dimeric bacterial Cu, Zn superoxide dismutases, in turn helping to explain the convergent evolution toward a dimeric structure in prokaryotic and eukaryotic enzymes of this class.

WOS: 000386404600009, In this study, an improved synthesis of 1,5-bis(2-formylphenyl)-1,5-dithiapentane(3) has been performed according to the literature in a high yield. 1,5-Bis (2-benzyl alcohol)-1,5-dithia pentane (4) was prepared by the reduction reaction of precursor compound in high yield via solvent-free conditions. Treatment of substituted benzylic alcohol with bromotrimethylsilane in dry acetonitrile in the presence of NaI resulted the formation of desired iodine derivative (5) in very high yield. 7,8-dihydro-6H, 14H, 19H-dibenzo[bj] [1,12,5,8]tetradithiacyclopentadecine-16,17-dicarbonitrile (7) was synthesized by the reaction of compound 7 and dithiomaleonitrile disodium salt. Magnesium porphyrazine carrying symmetrically four 15 membered tetrathia macro-cycles has been synthesized by the cyclotetramerization reaction of dicarbodinitrile compound (7) in the presence of magnesium butoxide according to the Linstead procedure. We focused on the prediction of the geometry optimization, normal mode frequencies, UV absorption spectra, chemical shifts and electronic properties of the compound by using B3LYP method with 6-31G(d) basis set. These novel compounds were characterized by a combination of elemental analysis, H-1, C-13 NMR, FTIR, UV vis and MS spectral data. An X-ray crystal structure of dicarbodinitrile compound (7) is also presented. The computed results are very close to the obtained experimental results by spectroscopic techniques, TUBITAK, The numerical calculations reported in this paper were partially performed at TUBITAK ULAKBIM, High Performance and Grid Computing Center (TRUBA resources). One of the author (B.Y) is also indepted to TUBITAK for financial support as scholarship. We are also grateful to Gebze Technical University X-Ray Center for the X-Ray data they provided.

A series of 6,7-disubstituted-3-{2-[4-(substituted)piperazin-1-yl]-2-oxoethyl}quinazoline- 2,4(1H,3H)-dione derivatives (7-34) were synthesized and their structures were elucidated on the basis of analytical and spectral (UV, IR, 1H-NMR, 13C-NMR and MS) data. These synthesized compounds were evaluated for their in vitro cytotoxicities against a panel of three human cancer cell lines. According to the cytotoxicity screening results, 3-{2-[4-(4-chlorobenzyl)piperazin-1-yl]-2-oxoethyl} quinazoline-2,4(1H,3H)-dione (7) presented the highest activity against HUH-7, MCF-7 and HCT-116 cell line with the IC50 values of 2.5, 6.8 and 4.9 µM, respectively. © 2016 Bentham Science Publishers.

Quinazolin-1-oxides were prepared by the oxidation of tetrahydroquinazolines with H 2 O 2 –tungstate and their ambient light photochemistry was investigated. Substituent effects on their photochemical cyclization and the reactions of the products 1a H -[1,2]oxazireno[2,3- a ]quinazolines under photochemical and thermal conditions are reported. The cyclization of quinazolin-1-oxides and the reactions of 1a H -[1,2]oxazireno[2,3- a ]quinazolines show pronounced solvent isotope and solvent effects.

The unknown effects of a receptor's environment on a ligand's conformation presents a difficult challenge in predicting feasible bioactive conformations, particularly if the receptor is ill-defined. The primary hypothesis of this work is that a structure's conformational ensemble in solution presents viable candidates for protein binding. The experimental solution profile can be achieved with the NAMFIS (NMR analysis of molecular flexibility in solution) method, which deconvolutes the average NMR spectrum of small flexible molecules into individual contributing conformations with varying populations. Geldanamycin and radicicol are structurally different macrocycles determined by X-ray crystallography to bind to a common site on the cellular chaperone heat shock protein 90 (Hsp90). Without benefit of a receptor structure, NAMFIS has identified the bioactive conformers of geldanamycin and radicicol in CDCl3 solution with populations of 4% and 21%, respectively. Conversely, docking the set of NAMFIS conformers into the unliganded proteins with GLIDE followed by MM-GBSA scoring reproduces the experimental crystallographic binding poses.

In the present paper, we report the synthesis, characterization, and biological evaluation as antifungal, antibacterial, antioxidant, and cytotoxic/anticancer agents of N-, S-, O-substituted-1,4-naphtho- and 2,5-bis(amino-substituted)-1,4-benzoquinone derivatives. In the synthesized compounds, antimicrobial activity at low concentrations against Escherichia coli B-906, Staphylococcus aureus 209-P, and Mycobacterium luteum B-917 bacteria and Candida tennis VKM Y-70 and Aspergillus niger F-1119 fungi in comparison with controls was identified. 2-(N-Diphenylmethylpiperazin-1-yl)-3-chloro-1,4-naphthoquinone 9a was the most potent, with a minimum inhibitory concentration value of 3.9, mu g/mL against test culture M. luteum. The synthesized compounds were screened for their antioxidant capacity using the cupric-reducing antioxidant capacity (CUPRAC) method. 2,2'-[1-(2-Aminoethyl)piperazin-1-yl]-3,3'-dichloro-bis(1,4-naphthoquinone) 10 showed the highest antioxidant capacity, with a 0.455 CUPRAC-trolox equivalent antioxidant capacity (TEAC) coefficient. Other parameters of antioxidant activity (scavenging effects on OH center dot, O-2(center dot-), and H2O2) of these compounds were also determined. The cytotoxic activity of the compounds was investigated by employing the sulforhodamine B cell viability assay against A549 (lung), MCF-7 (breast), DU145 (prostate), and HT-29 (colon) cancer cell lines. Compound 10 exhibited the most powerful cytotoxic activity at a concentration of 20 mu m against all cell lines. In addition to the strongest antioxidant activity of compound 10, it also had lowest IC50 values (

Synthesis of naturally occurring 6-(α,β-dihydrocinnamoyl)-3,4-dihydro-2H-chromanes has been carried out by the reaction of 6-acetyl-3,4-dihydro-2H--chromanes with methoxybenzaldehydes followed by hydrogenation of the resulting 6-cinnamoyl-3,4-dihydro-2H--chromanes.

The reaction of 2,4-diferrocenyl-1,3-dithiadiphosphetane 2,4-disulfide [FcPS(μ-S)]2 [Fc = Fe(η5-C5H4)(η5-C5H5)] with alcohols ROH gave the corresponding ferrocenyldithiophosphonic acids [FcPS(OR)(SH)], which were treated in situ with Ni(CH3COO)2·4H2O in acetic acid to yield the square-planar heterobimetallic trinuclear complexes [{FcP(OR)S2}2Ni] (R = Me (1), Et (2), Pri (3), Bus (4) and Bui (5)). Compounds 1-5 were characterized by elemental analysis, MS, NMR (1H, 13C and 31P), IR spectroscopy, and 2-5 also by X-ray crystallography. Cyclovoltammetric studies on the heterobimetallic nickel(II) complexes 1-5 showed irreversible reduction to unstable nickel(I) complexes and an irreversible two-electron oxidation of the sulfur-containing nickel fragments, followed by a reversible one-electron oxidation of the two ferrocenyl groups. Die Umsetzung von 2,4-Diferrocenyl-1,3-dithiadiphosphetan-2,4-disulfid [FcPS(μ-S)]2 [Fc = Fe(η5-C5H4)(η5-C5H5)] mit Alkoholen ROH liefert die entsprechenden Ferrocenyldithiophosphon-Sauren [FcPS(OR)(SH)], die in situ mit Ni(CH3COO)2·4H2O in Essigsaure zu den planar-quadratischen heterobimetallischen trinuklearen Komplexen [{FcP(OR)S2}2Ni] (R = Me (1), Et (2), Pri (3), Bus (4) and Bui (5)) umgesetzt wurden. Die Verbindungen 1-5 wurden durch Elementaranalyse, NMR (1H, 13C und 31P) und IR-Spektroskopie und durch Massenspektrometrie, 2-5 auch rontgenstrukturanalytisch charakterisiert. Cyclovoltammetrische Untersuchungen der heterobimetallischen Nickel(II)-Komplexe 1-5 zeigen die irreversible Reduktion zu instabilen Nickel(I)-Komplexen und die irreversible Zweielektronen-Oxidation des schwefelhaltigen Nickelkomplexfragments, gefolgt von einer reversiblen Einelektronen-Oxidation der beiden Ferrocenyl-Gruppen.

Dialkyltin(IV) and trialkyltin(IV) complexes of the deacetoxycephalo-sporin-antibiotic cephalexin [7-( d -2-amino-2-phenylacetamido)-3-methyl-3-cephem-4-carboxylic acid] (Hceph) have been synthesized and investigated both in solid and solution phase. Analytical and thermogravimetric data supported the general formula Alk 2 SnOHceph · H 2 O and Alk 3 Snceph · H 2 O (Alk=Me, n -Bu), while structural information has been gained by FT-IR, 119 Sn Mossbauer and 1 H, 13 C, 119 Sn NMR data. In particular, IR results suggested polymeric structures both for Alk 2 SnOHceph · H 2 O and Alk 3 Snceph · H 2 O. Moreover, cephalexin appears to behave as monoanionic tridentate ligand coordinating the tin(IV) atom through ester-type carboxylate, as well as through β-lactam carbonyl oxygen atoms and the amino nitrogen donor atoms in Alk 2 SnOHceph · H 2 O complexes. On the basis of 119 Sn Mossbauer spectroscopy it could be inferred that tin(IV) was hexacoordinated in such complexes in the solid state, showing skew trapezoidal configuration. As far as Alk 3 Sn(IV)ceph · H 2 O derivatives are concerned, cephalexin coordinated the Alk 3 Sn moiety through the carboxylate acting as a bridging bidentate monoanionic group. Again, 119 Sn Mossbauer spectroscopy led us to propose a trigonal configuration around the tin(IV) atom, with R 3 Sn equatorial disposition and bridging carboxylate oxygen atoms in the axial positions. The nature of the complexes in solution state was investigated by using 1 H, 13 C and 119 Sn NMR spectroscopy. Finally, the cytotoxic activity of organotin(IV) cephalexinate derivatives has been tested using two different chromosome-staining techniques Giemsa and CMA 3 , towards spermatocyte chromosomes of the mussel Brachidontes pharaonis (Mollusca: Bivalvia). Colchicinized-like mitoses (c-mitoses) on slides obtained from animals exposed to organotin(IV) cephalexinate compounds, demonstrated the high mitotic spindle-inhibiting potentiality of these chemicals. Moreover, structural damages such as ‘chromosome achromatic lesions’, ‘chromosome breakages’ and ‘chromosome fragments’ have been identified through a comparative analysis of spermatocyte chromosomes from untreated specimens (negative controls) and specimens treated with the organotin(IV) complexes.

New organic reactions allow chemical transformations which were previously not possible. Therefore, new reactions are important contributions to the progress in the field of organic synthesis. In this series we describe the design, scope, and limitations of newly-discovered multi-component reactions (MCRs). Herein, a first example of a MCR is introduced which allows general access to the class of 2,4-di- and 2,4,5-trisubstituted thiazoles.

New organic reactions allow chemical transformations which were previously not possible. Therefore, new reactions are important contributions to the progress in the field of organic synthesis. In this series we describe the design, scope, and limitations of newly-discovered multi-component reactions (MCRs). Herein, a first example of a MCR is introduced which allows general access to the class of 2,4-di- and 2,4,5-trisubstituted thiazoles.

The reactions of the precursor [Pd(N,C-dmba)(MeCN)2](NO3) (1) (dmba = N,N-dimethylbenzylamine), with the proligands 3,5-dimethylpyrazole (Hdmpz), 2-quinolinethiol (qnSH) and 1,1'-bis(diphenylphosphine)ferrocene (dppf) afforded the compounds [Pd(N,C-dmba)(Hdmpz)(ONO2)]0.5CH2 Cl2 (2), [Pd(N,C-dmba)(qnSH)(ONO2)] 0.5CH2Cl2 (3) and [Pd(N,C-dmba)(dppf)](NO3) (4), respectively. The mononuclear species 2, 3 and 4 were characterized by elemental analysis, infrared spectroscopy, NMR and thermogravimetric analysis. The IR spectra show bands which are consistent with terminal monodentate nitrate group for 2-3 and ionic nitrate for 4. The ¹H and 13C NMR data confirm that coordination of the organic ligands has occurred and the 31P{¹H} NMR data for 4 clearly evidences the occurrence in solution of three cyclopalladated species with the dppf acting as a bridging ligand in two cases and as a chelate in one. The thermal behavior of compounds 1-4 suggests that complex 2 is the most stable. The X-ray diffractometry results show the formation of PdO from 1 and 2, Pd2OSO4 from 3, and of a mixture of PdO and Fe2(PO4)3 from 4, as final decomposition products. As reações do ciclopaladado catiônico [Pd(N,C-dmba)(MeCN)2](NO3) (1) (dmba = N,N-dimetilbenzilamina), como os pré-ligantes 3,5-dimetilpirazol (Hdmpz); 2-quinolinatiol (qnSH) e 1,1'-bis(difenilfosfina)ferroceno (dppf) levaram à formação dos compostos, respectivamente, [Pd(N,C-dmba)(Hdmpz)(ONO2)]0.5CH2 Cl2 (2), [Pd(N,C-dmba)(qnSH)(ONO2)] 0.5CH2Cl2 (3) e [Pd(N,C-dmba)(dppf)](NO3) (4). As novas espécies mononucleares 2, 3 e 4 foram caracterizadas através de análise elementar, espectroscopia de absorção na região do infravermelho, espectroscopia de ressonância magnética nuclear e análise termogravimétrica. Os dados da espectroscopia no IV mostram bandas consistentes com o grupo nitrato monodentado nos casos dos compostos 2 e 3 e nitrato iônico no da espécie 4. Os dados de RMN de 13C e ¹H confirmam que os respectivos ligantes encontram-se coordenados ao átomo de paládio e o RMN de 31P{¹H} de 4 evidencia claramente a ocorrência de três espécies ciclopaladadas em solução, com o dppf atuando como ligante ponte em duas e como um quelato em uma. O comportamento térmico dos compostos 1-4 sugere que o composto 2 é o mais estável. Os resultados da difratometria de raios X, método do pó, confirmam a formação dos seguintes resíduos finais de termodecomposição: PdO para as espécies 1 e 2, uma mistura de PdO e Fe2(PO4)3 para 4 e, Pd2OSO4 para o composto 3.

Three diorganotin(IV) complexes of D-galacturonic acid (H2GalA; R = Me, n-Bu, Ph), two of which are new derivatives (R = Me, Ph), have been synthesized and their solid-state and solution-phase investigated by IR, Mossbauer, 1H, 13C and 119Sn NMR spectroscopy. The FTIR data suggest that H2GalA, in the dialkyltin derivatives, behaves as a dianionic ligand, coordinating the tin(IV) atom through an ester-type carboxylate and deprotonated alcoholic hydroxo groups, whereas a bridging carboxylate occurs in the diphenyltin(IV) complex. Octahedral and trigonal bipyramidal local geometries on tin(IV) atoms are proposed for dialkyltin(IV)GalA and diphenyltin(IV)GalA complexes respectively on the basis of Mossbauer spectroscopy. In D2O solution, R2Sn(IV) moieties seem to be mainly coordinated by the GalA2− in the β-furanosidic (β-GalfA2−) form, involving the β-furanosidic ring in rotational equilibrium. However, the α-furanosidic (α-GalfA2−), α-pyranosidic (α-GalpA2−) and the β-pyranosidic (β-GalpA2−) isomers are also involved in the coordination upon the tin atom to a minor extent. In DMSO-d6 solution, R2Sn(IV) moieties are coordinated almost entirely by the GalA2− in the β-furanosidic form. Copyright © 2003 John Wiley & Sons, Ltd.

Some 4-piperidinol derivatives were synthesized and their cytotoxicity was tested against human hepatoma (Huh7) and breast cancer (T47D) cells. Aryl part was changed as phenyl in 2a, 4-methylphenyl in 2b, 4-methoxyphenyl in 2c, 4-chlorophenyl in 2d, 4-fluorophenyl in 2e, 4-bromophenyl in 2f, 4-nitrophenyl in 2g and 2-thienyl in 3. Compounds were synthesized and reported for the first time by this study except 2a and 2d. Chemical structures were confirmed by 1H NMR, 13C NMR, IR, MS and elemental analyses. Compounds 2a (3.1 times), 2c (3.8 times), 2f (4.6 times), 2g (1.3 times) and 3 (3.2 times) had 1.3-4.6 times higher cytotoxic potency than the reference compound 5-FU against Huh7 cell line while all the compounds synthesized had shown lower activities against T47D cell line than 5-FU. In the light of these results, compounds 2a, 2c, 2f, 2g and 3 may serve as model compounds for further studies. © 2014 Informa UK Ltd.

The already known Ag(I)-Sb(III) compound of the formula {Ag(Ph3Sb)3(NO3)} (1) and two novel mixed metal Ag(I)-Sb(III) metallotherapeutics of the formulae {Ag(Ph3Sb)3(SalH)}(2) and {Ag(Ph3Sb)3(Asp)}(3) (SalH2 = salicylic acid, AspH = aspirin or 2-acetylsalicylic acid and Ph3Sb = triphenyl antimony(III)) have been synthesised and characterised by m.p., vibrational spectroscopy (mid-FT-IR), 13C-,1H-NMR, UV-visible (UV-vis) spectroscopic techniques, high resolution mass spectroscopy (HRMS) and X-ray crystallography. Compounds 1,- 3 were treated with the surfactant cetyltrimethylammonium bromide (CTAB) in order to enhance their solubility and as a consequence their bioactivity. The resulting micelles a-c were characterised with X-ray powder diffraction (XRPD) analysis, X-ray fluorescence (XRF) spectroscopy, Energy-dispersive X-ray spectroscopy (EDX), conductivity, Thermal gravimetry-differential thermal analysis (TG-DTA), and atomic absorption. Compounds 1-3 and the relevant micelles a-c were evaluated for their in vitro cytotoxic activity against human cancer cell lines: MCF-7 (breast, estrogen receptor (ER) positive), MDA-MB-231 (breast, ER negative) and MRC-5 (normal human fetal lung fibroblast cells) with sulforhodamine B (SRB) colorimetric assay. The results show significant increase in the activity of micelles compared to that of the initial compounds. Moreover, micelles exhibited lower activity against normal cells than tumor cells. The binding affinity of a-c towards the calf thymus (CT)-DNA, lipoxygenase (LOX) and glutathione (GSH) was studied by the fluorescent emission light and UV-vis spectroscopy. © 2015 Elsevier Inc. 150 108 119 Manufacturers: Sigma Aldrich Cited By :4

The marine sponge-derived fungus Auxarthron reticulatum produces the cannabinoid receptor antagonist amauromine (1). Recultivation of the fungus to obtain further amounts for more detailed pharmacological evaluation of 1 additionally yielded the novel triterpene glycoside auxarthonoside (2), bearing, in nature, a rather rare sugar moiety, i.e., N-acetyl-6-methoxy-glucosamine. Amauromine (1), which inhibited cannabinoid CB1 receptors (Ki0.178µM) also showed antagonistic activity at the cannabinoid-like orphan receptor GPR18 (IC50 3.74µM). The diketopiperazine 1 may thus serve as a lead structure for the development of more potent and selective GPR18 antagonists, which are required to study the orphan receptor's potential as a new drug target. Despite the execution of many biological assays, to date, no bioactivity could be found for auxarthonoside (2). © Georg Thieme Verlag KG Stuttgart · New York.