- Diamine derivative anti-Trichomonas vaginalis and anti-Tritrichomonas foetus activities by effect on polyamine metabolism
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Human and bovine trichomoniasis are sexually transmitted diseases (STD) caused by Trichomonas vaginalis and Tritrichomonas foetus, respectively. Human trichomoniasis is the most common non-viral STD in the world and bovine trichomoniasis causes significant economic losses to breeders. Considering the significant impact of the infections caused by these protozoa and the treatment failures, the search for new therapeutic alternatives becomes crucial. In this study the effect of diamines and amino alcohols in the in vitro viability of trichomonads was evaluated. Screening demonstrated the high activity of diamine 4 against these protozoa. Although cytotoxicity against HMVII cell line and slight hemolysis were observed in vitro, the compound showed no toxic effect on the Galleria mellonella in vivo model. Importantly, diamine 4 was active against both trichomonads species at 6 h and 24 h of incubation, and these effects was reverted by putrescine, a polyamine, suggesting competition for the same metabolic pathway. These findings indicate that the mechanism of action of diamine 4 is through the polyamine metabolism, a pathway distinct from that presented by metronidazole, the drug usually used to treat trichomoniasis and to which resistance is widely reported. These data demonstrate the importance of diamines as potential novel candidates as anti-T. vaginalis and anti-T. foetus agents.
- Rigo, Graziela Vargas,Trein, Márcia Rodrigues,da Silva Trentin, Danielle,Macedo, Alexandre José,de Oliveira, Bruno Assis,de Almeida, Angelina Maria,Giordani, Raquel Brandt,de Almeida, Mauro Vieira,Tasca, Tiana
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- New catanionic surfactants based on 1-alkyl-3-methylimidazolium alkylsulfonates, [CnH2n+1mim][CmH 2m+1SO3]: Mesomorphism and aggregation
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Anionic and cationic alkyl-chain effects on the self-aggregation of both neat and aqueous solutions of 1-alkyl-3-methylimidazolium alkylsulfonate salts ([CnH2n+1mim][CmH2m+1SO 3]; n = 8, 10 or 12; m = 1 and n = 4 or 8; m = 4 or 8) have been investigated. Some of these salts constitute a novel family of pure catanionic surfactants in aqueous solution. Examples of this class of materials are rare; they are distinct from both mixed cationic-anionic surfactants (obtained by mixing two salts) and gemini surfactants (with two or more amphiphilic groups bound by a covalent linker). Fluorescence spectroscopy and interfacial tension measurements have been used to determine critical micelle concentrations (CMCs), surface activity, and to compare the effects of the alkyl-substitution patterns in both the cation and anion on the surfactant properties of these salts. With relatively small methylsulfonate anions (n = 8, 10 and 12, m = 1), the salts behave as conventional single chain cationic surfactants, showing a decrease of the CMC upon increase of the alkyl chain length (n) in the cation. When the amphiphilic character is present in both the cation and anion (n = 4 and 8, m = 4 and 8), novel catanionic surfactants with CMC values lower than those of the corresponding cationic analogues, and which exhibited an unanticipated enhanced reduction of surface tension, were obtained. In addition, the thermotropic phase behaviour of [C8H18mim][C8H 18SO3] (n = m = 8) was investigated using variable temperature X-ray scattering, polarising optical microscopy and differential scanning calorimetry; formation of a smectic liquid crystalline phase with a broad temperature range was observed. the Owner Societies 2009.
- Blesic, Marijana,Swadzba-Kwasny, Malgorzata,Holbrey, John D.,Canongia Lopes, Jose N.,Seddon, Kenneth R.,Rebelo, Luis Paulo N.
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Read Online
- Enantiomeric synthesis of natural alkylglycerols and their antibacterial and antibiofilm activities
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Alkylglycerols (AKGs) are bioactive natural compounds that vary by alkyl chain length and degree of unsaturation, and their absolute configuration is 2S. Three AKGs (5l–5n) were synthesised in enantiomerically pure form, and were characterised for the first time together with 12 other known and naturally occurring AKGs (5a–5k, 5o). Their structures were established using 1H and 13C APT NMR with 2D-NMR, ESI-MS or HRESI-MS and optical rotation data, and they were tested for their antibacterial and antibiofilm activities. AKGs 5a–5m and 5o showed activity against five clinical isolates and P. aeruginosa ATCC 15442, with MIC values in the range of 15–125 μg/mL. In addition, at half of the MIC, most of the AKGs reduced S. aureus biofilm formation in the range of 23%–99% and P. aeruginosa ATCC 15442 biofilm formation in the range of 14%–64%. The antibiofilm activity of the AKGs assessed in this work had not previously been studied.
- Fernández Montoya, Deicy J.,Contreras Jordan, Luis A.,Moreno-Murillo, Bárbara,Silva-Gómez, Edelberto,Mayorga-Wandurraga, Humberto
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p. 2544 - 2550
(2019/11/13)
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- Synthesis method of special-pulling universal intermediate (by machine translation)
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To the invention, 9 - 2, 2, 6 tetramethylpiperidine oxide (TEMPO) is used as an oxidizing agent, the reaction temperature 6 - is lower, Fmoc-Cl is protected and oxidized to obtain N - (0 °C fluorenylmethoxycarbonyl) decyl aminoacetaldehyde. TEMPO oxidation is simple, the reaction temperature is mild, pH value and reaction temperature of the reaction liquid are controlled. (by machine translation)
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Paragraph 0024; 0039-0042
(2020/06/20)
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- VANCOMYCIN DERIVATIVE, PREPARATION METHOD, PHARMACEUTICAL COMPOSITION AND USE THEREOF
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Provided are a class of vancomycin derivatives with a structure as shown in the general formula below and pharmaceutically acceptable salts thereof, a preparation method, a pharmaceutical composition containing the compound thereof, and the use of these compounds in preparing drugs for treating and/or preventing bacterial infection diseases, in particular drugs for treating infection diseases caused by Gram-positive bacteria.
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Paragraph 0041; 0047; 0048
(2019/03/13)
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- Extra Sugar on Vancomycin: New Analogues for Combating Multidrug-Resistant Staphylococcus aureus and Vancomycin-Resistant Enterococci
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Lipophilic substitution on vancomycin is an effective strategy for the development of novel vancomycin analogues against drug-resistant bacteria by enhancing bacterial cell wall interactions. However, hydrophobic structures usually lead to long elimination half-life and accumulative toxicity; therefore, hydrophilic fragments were also introduced to the lipo-vancomycin to regulate their pharmacokinetic/pharmacodynamic properties. Here, we synthesized a series of new vancomycin analogues carrying various sugar moieties on the seventh-amino acid phenyl ring and lipophilic substitutions on vancosamine with extensive structure-activity relationship analysis. The optimal analogues indicated 128-1024-fold higher activity against methicillin-susceptible S. aureus, vancomycin-intermediate resistant S. aureus (VISA), and vancomycin-resistant Enterococci (VRE) compared with that of vancomycin. In vivo pharmacokinetics studies demonstrated the effective regulation of extra sugar motifs, which shortened the half-life and addressed concerns of accumulative toxicity of lipo-vancomycin. This work presents an effective strategy for lipo-vancomycin derivative design by introducing extra sugars, which leads to better antibiotic-like properties of enhanced efficacy, optimal pharmacokinetics, and lower toxicity.
- Guan, Dongliang,Chen, Feifei,Xiong, Lun,Tang, Feng,Faridoon,Qiu, Yunguang,Zhang, Naixia,Gong, Likun,Li, Jian,Lan, Lefu,Huang, Wei
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supporting information
p. 286 - 304
(2018/02/10)
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- FLUOROPOLYMER EMULSIONS WITH PERHALOGENATED STABILIZER FOR THE DELIVERY OF HYDROPHOBIC DRUGS
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The present invention provides therapeutic formulations, including therapeutic nanoemulsions, and related methods for the in vivo delivery of hydrophobic compounds, including an important class of hydrophobic anesthetics. Formulations and methods of the invention include semifluorinated block copolymers and perhalogenated fluorous compounds, such as perfluorooctyl bromide or perfluorodecalin, capable of forming a stable nanoemulsion without the need of conventional lipid components that support bacterial and/or fungal growth (e.g., soybean oil and similar lipids). In certain embodiments, emulsion-based formulations are provided that are capable of formulating, delivering and releasing amounts of hydrophobic drugs effective for a range of clinical applications, including inducing and maintaining anesthesia in patients. In certain embodiments, emulsion-based formulations are provided that are capable of supporting controlled release, for example, over a range of rates useful for clinical applications including rapid and sustained release.
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Paragraph 0143
(2015/11/16)
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- FLUOROPOLYMER EMULSIONS WITH BRANCHED SEMIFLUORINATED BLOCK COPOLYMER OR PHOSPHOLIPID SURFACTANT FOR THE DELIVERY OF HYDROPHOBIC DRUGS
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The present invention provides therapeutic formulations, including therapeutic nanoemulsions, and related methods for the in vivo delivery of hydrophobic compounds, including an important class of hydrophobic anesthetics. Formulations and methods of the invention include semifluorinated block copolymers, and optionally phospholipid surfactants, capable of forming a stable nanoemulsion without the need of conventional lipid components that support bacterial and/or fungal growth(e.g., soybean oil and similar lipids). In certain embodiments, emulsion-based formulations are provided that are capable of formulating, delivering and releasing amounts of hydrophobic drugs effective for a range of clinical applications, including inducing and maintaining anesthesia in patients. In certain embodiments, emulsion-based formulations are provided that are capable of supporting controlled release, for example, over a range of rates useful for clinical applications including rapid and sustained release.
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Paragraph 0172
(2015/11/10)
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- Synthesis, Physicochemical Characterization, and Self-Assembly of Linear, Dibranched, and Miktoarm Semifluorinated Triphilic Polymers
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Linear, dibranched, and miktoarm amphiphiles containing both hydrophobic and fluorophilic moieties were synthesized and characterized in an attempt to elucidate the relationship between semifluorinated amphiphile structure and aggregate behavior in aqueous solution. For the linear and dibranched amphiphiles, there was an exponential decrease in critical aggregation concentration (CMC) and a logarithmic increase in core microviscosity with increasing length of the fluorocarbon segments; while the miktoarm architecture produced no notable trend in microviscosity or CMC. Furthermore, the linear and dibranched surfactants showed enhanced kinetic stability, dissociating more slowly in the presence of human serum than did either the dibranched or miktoarm amphiphiles. Finally, encapsulation studies with the hydrophobic drug paclitaxel (PTX) showed that the ability to solubilize and retain PTX increased with the presence and with the increasing size of the fluorocarbon moiety for both the linear and dibranched amphiphiles, while no such trend was observed for the miktoarm amphiphiles. VC 2014 Wiley Periodicals, Inc.
- Tucker, William B.,McCoy, Aaron M.,Fix, Samantha M.,Stagg, Melissa F.,Murphy, Matt M.,Mecozzi, Sandro
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p. 3324 - 3336
(2015/02/05)
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- Novel antiviral activity of l-dideoxy bicyclic nucleoside analogues versus vaccinia and measles viruses in vitro
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Dideoxy bicyclic pyrimidine nucleoside analogues (ddBCNAs) with d-chirality have previously been described by us to inhibit replication of human cytomegalovirus. We herein report for the first time that activity against vaccinia virus (VACV) was achieved
- McGuigan, Christopher,Hinsinger, Karen,Farleigh, Laura,Pathirana, Ranjith N.,Bugert, Joachim J.
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p. 1311 - 1322
(2013/03/29)
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- Synthesis and antileishmanial activity of lipidic amino alcohols
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In this work, a number of lipidic amino alcohols wereas synthesized and evaluated in vitro on cultures of Leishmania amazonensis and Leishmania chagasi. Nine amino alcohols showed inhibition of L. chagasi growth, and seven of them showed inhibition of L. amazonensis with IC50 below 10 μm. Compound 11f was more active than the reference drug amphotericin B against L. chagasi promastigote forms.
- Coimbra, Elaine S.,De Almeida, Mauro V.,Junior, Celso O. R.,Taveira, Aline F.,Da Costa, Cristiane F.,De Almeida, Ana C.,Reis, Elaine F. C.,Da Silva, Adilson D.
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scheme or table
p. 233 - 235
(2010/12/20)
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- Nanostructures in ionic liquids: Correlation of iridium nanoparticles' size and shape with imidazolium salts' structural organization and catalytic properties
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Hydrogen reduction of cationic or neutral Ir(i) compounds, namely [Ir(COD)2]BF4 and [Ir(COD)Cl]2respectively. in the ionic liquid (IL) 1-alkyl-3-methylimidazolium tetrafluoroborate affords either irregularly sized spherical (from 1.9 ± 0.4 to 3.6 ± 0.9 nm) or worm-like metal nanoparticles, depending on the nature of the imidazolium alkyl group and the type of iridium precursor. The ionic Ir(i) precursor tends to be dissolved and concentrated on the IL polar domains (populated by the imidazolium nucleus and tetrafluoroborate anions) while the neutral precursor dissolves preferentially in the non-polar region of the IL (populated mainly by N-alkyl side chains). The size, or volume, of the nano-region where the Ir(i) precursor is dissolved and reduced, determines the size and, probably, the shape of the formed nanoparticles. The HR-TEM image shows that the Ir(0) with worm-like shape are polycrystalline and formed from aggregation individual "spherical" nanoparticles of around 1.9 nm. The catalytic activity of Ir(0) NPs on the hydrogenation of cyclohexene (0.01 mol L-1 of Ir atoms in IL, 75°C, 8 bar of H2, 500 rpm stirring, 1/1000 Ir(0)/cyclohexene ratio) is always greater in C1C 10I·BF4 than C1C4I· BF4, regardless of the nature of Ir(i) precursor. Moreover, the cyclohexene hydrogenations performed with Ir(0) nanocatalysts made from ionic Ir(i) precursor are approximately twice faster than those NPs obtained from the neutral Ir(i) precursor, in the same IL. the Owner Societies.
- Migowski, Pedro,Zanchet, Daniela,MacHado, Giovanna,Gelesky, Marcos A.,Teixeira, Sergio R.,Dupont, Jairton
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experimental part
p. 6826 - 6833
(2011/09/12)
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- A highly active catalyst supported molecular sieves-NaHCO3 mixture for the selective and advantageous N-monoalkylation of amines
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Amines are mono-N-alkylated by alkylmesylates in the presence of catalyst supported molecular sieves-NaHCO3 mixture in a regioselective, chemoselective and non-toxic process. Observed chemoselectivity is supported by 'DFT'.
- Das, Asish R.,Medda, Arunima,Singha, Raghunath,Guchhait, Nikhil
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experimental part
p. 841 - 848
(2010/06/01)
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- Direct functionalization of self-assembled nanotubes overcomes unfavorable self-assembling processes
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Diamides containing alkyne and azido were self-assembled into nanotubes and were reacted under their self-assembled state with small molecules by "click chemistry"; the resulting compounds remain self-assembled into new nanotubes that cannot be formed by
- Nguyen, Thi-Thanh-Tam,Simon, Franois-Xavier,Schmutz, Marc,Mesini, Philippe J.
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supporting information; experimental part
p. 3457 - 3459
(2009/12/26)
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- 1-Alkyl-3-methylimidazolium alkanesulfonate ionic liquids, [C nH2n+1mim][CkH 2k+1SO3]: Synthesis and physicochemical properties
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A set of 1-alkyl-3-methylimidazolium alkanesulfonate ionic liquids, [C nmim][CkSO3], formed by the variation of the alkyl chain lengths both in the cation and the anion (n = 1-6, 8, or 10; k = 1-4, or 6), was synthesised, with sixteen of them being novel. The ionic liquids were characterised by 1H and 13C NMR spectroscopy, and mass spectrometry. Their viscosities and densities as a function of temperature, as well as melting points and decomposition temperatures, were determined. The molecular volumes, both experimental and calculated, were found to depend linearly on the sum (n + k). the Owner Societies 2009.
- Blesic, Marijana,Swadzba-Kwasny, Malgorzata,Belhocine, Tayeb,Gunaratne, H. Q. Nimal,Lopes, Jose N. Canongia,Gomes, Margarida F. Costa,Padua, Agilio A. H.,Seddon, Kenneth R.,Rebelo, Luis Paulo N.
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experimental part
p. 8939 - 8948
(2010/06/20)
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- Preparation and antitubercular activities of alkylated amino alcohols and their glycosylated derivatives
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A series of N- and C-alkylated amino alcohols and of their protected galactopyranosyl derivatives was synthesized and evaluated for antitubercular activity. Five of these compounds displayed good activity, with a MIC below 12.5 μg/mL. The presence of the carbohydrate slightly affected the antibacterial activity.
- Taveira, Aline F.,Hyaric, Mireille Le,Reis, Elaine F.C.,Araujo, Debora P.,Ferreira, Ana Paula,de Souza, Maria Aparecida,Alves, Livia L.,Lourenco, Maria C.S.,Vicente, Felipe Rodrigues C.,de Almeida, Mauro V.
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p. 7789 - 7794
(2008/04/05)
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- Process for preparation of oxyglutaric acid ester derivatives
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A process for preparing an oxyglutaric acid ester derivative of the formula: STR1 in which each of R1 and R2 is C1-5 alkoxy, C1-7 aralkyloxy, C7-9 halogenated aralkyloxy or phenyl, R4 is a hydroxyl-protecting group, and R5 is C1-10 alkyl which may have a substituent, comprises the steps of reacting a methyl phosphonate derivative or methyl phosphine oxide derivative with an oxyglutaric acid mono-ester to give a reaction product which comprises an oxyglutaric acid derivative having a phosphorus-containing group and a pentenedioic acid mono-ester (by-product), removing the pendenedioic acid mono-ester from the reaction product to isolate the oxyglutaric acid derivative, and converting the isolated oxyglutaric acid derivative into the oxyglutaric acid ester derivative. A process for obtaining an optically active oxyglutaric acid ester derivative is also disclosed.
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- Benzophenone Dicarboxylic Acid Antagonists of Leukotriene B4. 2. Structure-Activity Relationships of the Lipophilic Side Chain
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A series of lipophilic benzophenone dicarboxylic acid derivatives were found to inhibit the binding of the potent chemotoxin leukotriene B4 (LTB4) to its receptor on intact human neutrophils.Activity at the LTB4 receptor was determined by using a 3H>LTB4-binding assay.The structure-activity relationship for the lipophilic side chain was systematically investigated.Compounds with n-alkyl side chains of varying lengths were prepared and tested.Best inhibition of 3H>LTB4 binding was observed with the n-decyl derivative.Analogues with alkyl chains terminated with an aromatic ring showed improved activity.The 6-phenylhexyl side chain was optimal.Substitution on the terminal aromatic ring was also evaluated.Methoxyl, methylsulfinyl, and methyl substituents greatly enhanced the activity of the compound.For a given substituent, the para isomer had the best activity.Thus the nature of the lipophilic side chain can greatly influence the ability of the compounds to inhibit the binding of LTB4 to its receptor on intact human neutrophils.The most active compound from this series, 84 (LY223982), bound to the LTB4 receptor with the affinity approaching that of the agonist.
- Gapinski, D. Mark,Mallett, Barbara E.,Froelich, Larry L.,Jackson, William T.
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p. 2807 - 2813
(2007/10/02)
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- 3,4-Bis(4-substituted piperazinyl)-3-cyclobutene-1,2-diones and related compounds
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3,4-bis(4-substituted piperazinyl)-3-cyclobutene-1,2-diones and related compounds having antiviral activity are described herein. The subject compounds can be prepared by reacting 3,4-dimethoxy-3-cyclobutene-1,2-dione with the appropriate substituted piperazine.
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