- Pseudotrienic acids A and B, two bioactive metabolites from Pseudomonas sp. MF381-IODS
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Bioassay-guided fractionation of the liquid culture broth of Pseudomonas sp. MF381-IODS yielded two new antimicrobial substances, identified as (2E,4E,6E)-9-[((2S,3R)-3-hydroxy-4-{(3E,5E,7RS)-7-hydroxy-4-methylhexadeca-3, 5-dienoyl]amino}-2-methylbutanoyl)amino]nona-2,4,6-trienoic acid and the tetradeca equivalent, named pseudotrienic acids A (1) and B (2), respectively. The compounds are prone to lactone formation, and their structures suggest them to be derived from ring opening of a macrolide. Pseudotrienic acids A and B inhibited growth of Staphylococcus aureus (MIC 70 μg/mL) and Pseudomonas syringae pv. syringae (MIC 70 μg/mL). Two known antimicrobial compounds, the polyketide 2,3-deepoxy-2,3-didehydrorhizoxin (3) and the tryptophan-derived pyrrolnitrin (4), were also identified.
- Pohanka, Anton,Broberg, Anders,Johansson, Maria,Kenne, Lennart,Levenfors, Jolanta
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Read Online
- Synthesis, computational studies and enzyme inhibitory kinetics of benzothiazole-linked thioureas as mushroom tyrosinase inhibitors
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Herein, we report synthesis of a set of benzothiazole-thiourea hybrids with aromatic and aliphatic side chains (BT1 to BT9) using an elegant synthetic strategy. The newly synthesized benzothiazole-thiourea conjugates were subjected to In-vitro tyrosinase inhibition and free radical scavenging activity. Majority of the compounds indicated inhibition considerably improved than the standard; compound (Kojic acid with IC50 = 16.8320 ± 1.1600 μM) BT2 with IC50 = 1.3431 ± 0.0254 μM was found to be the best inhibitor. A non-competitive mode of inhibition of BT2 was disclosed with Ki value of 2.8 μM. In order to study enzyme-inhibitor interactions SAR analysis molecular docking was carried out. The amino groups of thiourea were involved in hydrogen bonding with Glu322 showing the bond length of 1.74 and 2.70 ?, respectively. Moreover, the coupling of π-π was displayed between benzothiazole and benzene rings of His244 and His263, respectively. The outcome of this study might help to develop new inhibitors of melanogenesis, important for cosmetic and food products. Communicated by Ramaswamy H. Sarma.
- Ujan, Rabail,Saeed, Aamer,Ashraf, Saba,Channar, Pervaiz Ali,Abbas, Qamar,Rind, Mahboob Ali,Hassan, Mubashir,Raza, Hussain,Seo, Sung-Yum,El-Seedi, Hesham R.
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p. 7035 - 7043
(2020/08/12)
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- Benzimidazole tethered thioureas as a new entry to elastase inhibition and free radical scavenging: Synthesis, molecular docking, and enzyme inhibitory kinetics
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The porcine pancreatic elastase inhibition and free-radical scavenging play a crucial role in age progression. All the series of 10 newly synthesized benzimidazole thioureas (4a-j) were assessed for elastase inhibition and radical scavenging activity to identify the suitable anti-aging ingredient for cosmetics products. The compounds 4e, 4f, 4g, and 4h showed inhibition better than the standard, while compound 4f showed the most significant elastase inhibition with the IC50 value of 1.318 ± 0.025 μM compared with oleanic acid IC50 13.451 ± 0.014 used ±1.989 and 41.563 ± 0.824, respectively, as standard. Molecular docking studies were performed and the compound 4f showed binding energy of 7.2 kcal/mol. Kinetics studies revealed inhibition of the pancreatic elastase in a competitive manner. The relative binding energy and structure activity relationship (SAR) identified compound 4f as an effective inhibitor of porcine pancreatic elastase. Compounds 4e and 4i showed remarkable free-radical scavenging activity with SC50 values of 26.421.
- Abbas, Qamar,Ashraf, Saba,Channar, Pervaiz Ali,Hassan, Abbas,Hassan, Mubashar,Rafique, Hummera,Raza, Hussain,Rind, Mahboob Ali,Saeed, Aamer,Seo, Sung-Yum,Ujan, Rabail,Ul-Hamid, Anwar
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- L-ascorbyl 6-palmitate as lead compound targeting SphK1: an in silico and in vitro investigation
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Sphingosine kinases (SphKs) are a class of lipid kinases, that have received extensive attention as important rate-limiting enzyme in tumor. Inhibition of the activity of SphK1 can lead to an anticancer effect. Herein, we describe the discovery process and biological characteristics of a new SphK1 inhibitor, ascorbyl palmitate, discovered through computer-aided drug design. Biochemical experiments show that ascorbyl palmitate has a strong inhibitory effect on SphK1, with an IC50 value of 6.4 μM. The MTT experiment showed that ascorbyl palmitate had anti-cancer effects toward the U87, A549, 22RV1, and A375 cell lines. Among them, ascorbyl palmitate has prominent inhibitory activity against the 22RV1 cell line, with an IC50 value of 41.57 μM. To explore the structure–activity relationship, four ascorbyl palmitate derivatives were synthesized and tested for kinase activity. The outstanding effect of ascorbyl palmitate toward SphK1 and its known non-toxicity suggest that ascorbyl palmitate may be a lead compound for the development of effective SphK1 anti-cancer inhibitors.
- Chen, HaiJiao,Liu, Bo,Sun, Peng,Yang, Xinmei,Yao, Qingqiang,Zhi, Ying
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p. 781 - 787
(2021/04/05)
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- Neutrophil-Selective Fluorescent Probe Development through Metabolism-Oriented Live-Cell Distinction
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Human neutrophils are the most abundant leukocytes and have been considered as the first line of defence in the innate immune system. Selective imaging of live neutrophils will facilitate the in situ study of neutrophils in infection or inflammation events as well as clinical diagnosis. However, small-molecule-based probes for the discrimination of live neutrophils among different granulocytes in human blood have yet to be reported. Herein, we report the first fluorescent probe NeutropG for the specific distinction and imaging of active neutrophils. The selective staining mechanism of NeutropG is elucidated as metabolism-oriented live-cell distinction (MOLD) through lipid droplet biogenesis with the help of ACSL and DGAT. Finally, NeutropG is applied to accurately quantify neutrophil levels in fresh blood samples by showing a high correlation with the current clinical method.
- Gao, Min,Lee, Sun Hyeok,Park, Sang Hyuk,Ciaramicoli, Larissa Miasiro,Kwon, Haw-Young,Cho, Heewon,Jeong, Joseph,Chang, Young-Tae
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supporting information
p. 23743 - 23749
(2021/10/14)
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- Boosting the efficacy of anti-MRSA β-lactam antibiotics via an easily accessible, non-cytotoxic and orally bioavailable FtsZ inhibitor
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The rapid emergence of methicillin-resistant Staphylococcus aureus (MRSA) strains has undermined the therapeutic efficacy of existing β-lactam antibiotics (BLAs), prompting an urgent need to discover novel BLAs adjuvants that can potentiate their anti-MRSA activities. In this study, cytotoxicity and antibacterial screening of a focused compound library enabled us to identify a compound, namely 28, which exhibited low cytotoxicity against normal cells and robust in vitro bactericidal synergy with different classes of BLAs against a panel of multidrug-resistant clinical MRSA isolates. A series of biochemical assays and microscopic studies have revealed that compound 28 is likely to interact with the S. aureus FtsZ protein at the T7-loop binding pocket and inhibit polymerization of FtsZ protein without interfering with its GTPase activity, resulting in extensive delocalization of Z-ring and morphological changes characterized by significant enlargement of the bacterial cell. Animal studies demonstrated that compound 28 had a favorable pharmacokinetic profile and exhibited potent synergistic efficacy with cefuroxime antibiotic in a murine systemic infection model of MRSA. Overall, compound 28 represents a promising lead of FtsZ inhibitor for further development of efficacious BLAs adjuvants to treat the staphylococcal infection.
- Lui, Hok Kiu,Gao, Wei,Cheung, Kwan Choi,Jin, Wen Bin,Sun, Ning,Kan, Jason W.Y.,Wong, Iris L.K.,Chiou, Jiachi,Lin, Dachuan,Chan, Edward W.C.,Leung, Yun-Chung,Chan, Tak Hang,Chen, Sheng,Chan, Kin-Fai,Wong, Kwok-Yin
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- Utilization of hexabromoacetone for protection of alcohols and aldehydes and deprotection of acetals, ketals, and oximes under UV irradiation
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Hexabromoacetone (HBA) was efficiently used for the protection of alcohols and aldehydes and deprotection of benzaldehyde dimethyl acetal, solketal, and other acetals and ketals. In only 10?min, the protection of glycerol yielded 90% of solketal and protection of benzaldehyde gave 95% of benzaldehyde dimethyl acetal. The deprotection of benzaldehyde dimethyl acetal under UV irradiation gave over 90% yield of benzaldehyde within 15?s using only 2.5?mol% of HBA. HBA was also successfully used for deoximation. Solvent was found to play an important role in the efficiency of HBA for these reactions.
- Chaiseeda, Kittichai,Chantharadet, Ladawan,Chavasiri, Warinthorn
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p. 1305 - 1323
(2017/10/30)
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- IONIZABLE CATIONIC LIPID FOR RNA DELIVERY
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What is described is a compound of formula I consisting of a compound in which R1 is a branched chain alkyl consisting of 10 to 31 carbons; R2 is a linear alkyl, alkenyl, or alkynyl consisting of 2 to 20 carbons; L1 and L2 are the same or different, each a linear alkylene of 1 to 20 carbons or a linear alkenylene of 2 to 20 carbons; X1 is S or O; R3 is a linear or branched alkylene consisting of 1 to 6 carbons; and R4 and R5 are the same or different, each a hydrogen or a linear or branched alkyl consisting of 1 to 6 carbons; or a pharmaceutically acceptable salt thereof.
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Paragraph 0025; 0344; 0345
(2018/07/04)
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- Synthesis, Physicochemical Properties, and Thermo-Oxidative Stability of Diesters of 5,7-Dimethyl-1,3-Adamantanediol and 5,7-Dimethyl-1,3-bis(Hydroxymethyl)adamantane
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A series of diesters on the basis of 5,7-dimethyl-1,3-adamantanediol and 5,7-dimethyl-1,3- bis(hydroxymethyl)adamantane and C3–C10 aliphatic acids have been synthesized and their physicochemical and thermo-oxidative properties have been studied. The properties of the esters obtained have been compared to those of trimethylolpropane and neopentyl glycol esters.
- Ivleva,Baimuratov,Demidov,Lukashenko,Malinovskaya, Yu. A.,Klimochkin, Yu. N.,Tyshchenko,Kulikova,Pozdnyakov,Ovchinnikov,Rudyak
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p. 687 - 693
(2018/07/29)
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- Janus particles self-assembled from a small organic atypical asymmetric gemini surfactant
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A series of atypical asymmetric gemini surfactants with an amphiphilic carbonate group (-O-CO-O-) have been prepared. Some of these compounds could self-assemble in water into gourd-shaped Janus particles (JPs). Initial results suggested that the formation of JPs was highly likely to be related to their atypical gemini surfactant structure. To our knowledge, this is the first report on JPs that are self-assembled from a single kind of small organic molecule. We believe that our results will be utilized in many fields.
- Tang, Lei,Yang, Jun,Yin, Qinqin,Yang, Linghui,Gong, Deying,Qin, Feng,Liu, Junyang,Fan, Qin,Li, Jiahong,Zhao, Wenling,Zhang, Weiyi,Wang, Jiyu,Zhu, Tao,Zhang, Wensheng,Liu, Jin
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supporting information
p. 8675 - 8678
(2017/08/10)
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- Structure, supramolecular organization and phase behavior of N-acyl-β-alanines: Structural homologues of mammalian brain constituents N-acylglycine and N-acyl-GABA
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N-Acyl-β-alanines (NABAs) are structural homologues of N-acylglycines (NAGs) and N-acyl-γ-aminobutyric acids (NAGABAs), and achiral isomers of N-acylalanines, which are all present in mammalian brain and other tissues and modulate activity of biological receptors with various functions. In the present study, we synthesized and characterized a homologous series of NABAs bearing saturated acyl chains (n = 8-20) and investigated their supramolecular organization and thermotropic phase behavior. In differential scanning calorimetric (DSC) studies, most of the NABAs gave one or two minor transitions before the main chain-melting phase transition in the dry state as well as upon hydration with water, but gave only a single transition when hydrated with buffer (pH 7.6). Transition enthalpies (ΔHt) and entropies (ΔSt), obtained from the DSC studies showed linear dependence on the chain length in the dry state and upon hydration with buffer, whereas odd-even alteration was observed when hydrated with water. The crystal structures of N-lauroyl-β-alanine (NLBA) and N-myristoyl-β-alanine (NMBA) were solved in monoclinic system in the P21/c space group. Both NLBA and NMBA were packed in tilted bilayers with head-to-head (and tail-to-tail) arrangement with tilt angles of 33.28° and 34.42°, respectively. Strong hydrogen bonding interactions between [sbnd]COOH groups of the molecules from opposite leaflets as well as N[sbnd]H?O hydrogen bonds between the amide groups from adjacent molecules in the same leaflet as well as dispersion interactions between the acyl chains stabilize the bilayer structure. The d-spacings calculated from powder X-ray diffraction studies showed odd-even alteration with odd-chain length compounds exhibiting higher values as compared to the even-chain length ones and the tilt angles calculated from the PXRD data are higher for the even chain NABAs. These observations are relevant to developing structure-activity relationships for these amphiphiles and understand how NABAs differ from their homologues and isomers, namely NAGs, NAGABAs, and N-acylalanines.
- Sivaramakrishna,Swamy, Musti J.
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- An LC-MS/MS method to quantify acylcarnitine species including isomeric and odd-numbered forms in plasma and tissues
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Acylcarnitines are intermediates of fatty acid and amino acid oxidation found in tissues and body fluids. They are important diagnostic markers for inherited diseases of peroxisomal and mitochondrial oxidation processes and were recently described as biomarkers of complex diseases like the metabolic syndrome. Quantification of acylcarnitine species can become challenging because various species occur as isomers and/or have very low concentrations. Here we describe a new LC-MS/MS method for quantification of 56 acylcarnitine species with acyl-chain lengths from C2 to C18. Our method includes amino acid-derived positional isomers, like methacrylyl-carnitine (2-M-C3:1-CN) and crotonyl-carnitine (C4:1-CN), and odd-numbered carbon species, like pentadecanoyl-carnitine (C15:0-CN) and heptadecanoyl-carnitine (C17:0-CN), occurring at very low concentrations in plasma and tissues. Method validation in plasma and liver samples showed high sensitivity and excellent accuracy and precision. In an application to samples from streptozotocin-treated diabetic mice, we identified significantly increased concentrations of acylcarnitines derived from branched-chain amino acid degradation and of odd-numbered straight-chain species, recently proposed as potential biomarkers for the metabolic syndrome. In conclusion, the LC-MS/MS method presented here allows robust quantification of isomeric acylcarnitine species and extends the palette of acylcarnitines with diagnostic potential derived from fatty acid and amino acid metabolism.
- Giesbertz, Pieter,Ecker, Josef,Haag, Alexander,Spanier, Britta,Daniel, Hannelore
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p. 2029 - 2039
(2015/11/17)
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- Differential scanning calorimetric and powder X-ray diffraction studies on a homologous series of N-acyl-L-alanine esters with matched chains (n = 9-18)
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A homologous series of two chain derivatives of L-alanine, namely N-acyl L-alanine alkyl esters (NAAEs), bearing matched, saturated, acyl and alkyl chains (n= 9-18) have been synthesized. The thermotropic phase transitions and supramolecular structure of NAAEs were investigated by differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD). Results obtained from DSC studies indicate that the transition temperatures (T t), enthalpies (ΔH t) and entropies (ΔS t) exhibit odd-even alternation with compounds bearing odd acyl and alkyl chains showing higher values of T t, ΔH t and ΔS t as compared to NAAEs with even acyl and alkyl chains. However, the transition enthalpies and entropies of the odd- and even chain length series independently exhibit a linear dependence on the chain length. The d-spacings obtained from PXRD increase linearly with chain length with an increment of 1.76 ?/CH 2, suggesting that NAAEs adopt either a tilted bilayer structure or a bent structure. The present results provide a thermodynamic and structural basis for investigating the interaction of NAAEs with other membrane lipids, which in turn can shed light in understanding how they can enhance the transdermal permeability of stratum corneum.
- Sivaramakrishna,Swamy, Musti J.
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p. 1627 - 1635
(2015/12/01)
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- Metal-Free Direct Oxidation of Aldehydes to Esters Using TCCA
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Aromatic and aliphatic aldehydes are simply converted into esters by an efficient oxidative esterification carried out under mild conditions. The aldehydes are converted in situ into their corresponding acyl chlorides, which are then reacted with primary and secondary aliphatic, benzylic, allylic, and propargylic alcohols and phenols. A variety of esters are obtained in high yields.
- Gaspa, Silvia,Porcheddu, Andrea,De Luca, Lidia
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supporting information
p. 3666 - 3669
(2015/08/18)
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- Chiral Surfactant-Type Catalyst: Enantioselective Reduction of Long-Chain Aliphatic Ketoesters in Water
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A series of amphiphilic ligands were designed and synthesized. The rhodium complexes with the ligands were applied to the asymmetric transfer hydrogenation of broad range of long-chained aliphatic ketoesters in neat water. Quantitative conversion and excellent enantioselectivity (up to 99% ee) was observed for α-, β-, γ-, δ- and ε-ketoesters as well as for α- and β-acyloxyketone using chiral surfactant-type catalyst 2. The CH/π interaction and the strong hydrophobic interaction of long aliphatic chains between the catalyst and the substrate in the metallomicelle core played a key role in the catalytic transition state. Synergistic effects between the metal-catalyzed site and the hydrophobic microenvironment of the core in the micelle contributed to high stereoselectivity. (Chemical Equation Presented).
- Lin, Zechao,Li, Jiahong,Huang, Qingfei,Huang, Qiuya,Wang, Qiwei,Tang, Lei,Gong, Deying,Yang, Jun,Zhu, Jin,Deng, Jingen
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p. 4419 - 4429
(2015/05/13)
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- Total synthesis of capsaicin analogues from lignin-derived compounds by combined heterogeneous metal, organocatalytic and enzymatic cascades in one pot
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The total synthesis of capsaicin analogues was performed in one pot, starting from compounds that can be derived from lignin. Heterogeneous palladium nanoparticles were used to oxidise alcohols to aldehydes, which were further converted to amines by an enzyme cascade system, including an amine transaminase. It was shown that the palladium catalyst and the enzyme cascade system could be successfully combined in the same pot for conversion of alcohols to amines without any purification of intermediates. The intermediate vanillylamine, prepared with the enzyme cascade system, could be further converted to capsaicin analogues without any purification using either fatty acids and a lipase, or Schotten-Baumann conditions, in the same pot. An aldol compound (a simple lignin model) could also be used as starting material for the synthesis of capsaicin analogues. Using L-alanine as organocatalyst, vanillin could be obtained by a retro-aldol reaction. This could be combined with the enzyme cascade system to convert the aldol compound to vanillylamine in a one-step one-pot reaction.
- Anderson, Mattias,Afewerki, Samson,Berglund, Per,Cordova, Armando
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supporting information
p. 2113 - 2118
(2014/07/07)
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- Synthesis, characterization and biological evaluation of novel diesters of 4,4'-dihydroxy azoxy benzene with long chain carboxylic acids
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Synthesis of novel symmetrical azoxy diesters have been prepared by the reaction of 4,4'-dihydroxyazoxy benzene with aliphatic acid halides of varying chain lengths. The synthesized compounds have been characterized by spectral and analytical data. These symmetrical azoxy diesters exhibit good antifungal activity against six fungal strains (Mucor species, Aspergillus niger, Aspergillus flavus, Alternaria solani, Fusarium solani and Aspergillus fumigatus) and antitumor activities while no significant antibacterial activity has been observed. These synthesized compounds are also potent free radical scavengers.
- Shehzadi, Sumaira,Siddiqi, Humaira Masood,Qasim, Malik Muhammed,Fawad, Musfirah,Manan, Abdul,Khan, Naeema,Saleem, Samreen,Bashir, Farah,Mirza, Bushra
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p. 462 - 472
(2014/08/05)
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- Structure and thermotropic phase behavior of a homologous series of n -Acylglycines: Neuroactive and antinociceptive constituents of biomembranes
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N-Acylglycines (NAGs) with different acyl chains have been found in the mammalian brain and other tissues. They exhibit significant biological and pharmacological properties and appear to play important roles in communication and signaling pathways within and between cells. In view of this, a homologous series of NAGs have been synthesized and characterized in the present study. Differential scanning calorimetric (DSC) studies show that the transition enthalpies and entropies of dry as well as hydrated NAGs exhibit a linear dependence on the acyl chain length. Most of the NAGs show a minor transition below the chain-melting phase transition, suggesting the presence of polymorphism in the solid state. Structures of N-myristoylglycine (NMG) and N-palmitoylglycine (NPG) were solved in monoclinic system with C2/c and P21 space groups, respectively. Analysis of the crystal structures show that NAGs are organized in a bilayer fashion, with head-to-head (and tail-to-tail) arrangement of molecules. The acyl chains in both structures are essentially perpendicular to the bilayer plane, which is consistent with a lack of odd-even alternation in the thermodynamic properties. The bilayer is stabilized by strong hydrogen bonding interactions between COOH groups of the molecules from opposite leaflets as well as N-H···O hydrogen bonds between the amide groups of adjacent molecules in the same leaflet and dispersion interactions among the acyl chains. Powder X-ray diffraction data show that the d-spacings for the NAGs with different acyl chains (n = 8-20) exhibit a linear dependence on the chain length, suggesting that all the NAGs investigated here adopt a similar packing arrangement in the crystal lattice. These observations are relevant for understanding the role of N-acylglycines in biological membranes.
- Reddy, S. Thirupathi,Krovi, Krishna Prasad,Swamy, Musti J.
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p. 4944 - 4954
(2014/12/10)
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- Novel capsaicin analogues as potential anticancer agents: Synthesis, biological evaluation, and in silico approach
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A novel class of benzo[d][1,3]dioxol-5-ylmethyl alkyl/aryl amide and ester analogues of capsaicin were designed, synthesized, and evaluated for their cytotoxic activity against human and murine cancer cell lines (B16F10, SK-MEL-28, NCI-H1299, NCI-H460, SK-BR-3, and MDA-MB-231) and human lung fibroblasts (MRC-5). Three compounds (5f, 6c, and 6e ) selectively inhibited the growth of aggressive cancer cells in the micromolar (mM) range. Furthermore, an exploratory data analysis pointed at the topological and electronic molecular properties as responsible for the discrimination process regarding the set of investigated compounds. The findings suggest that the applied designing strategy, besides providing more potent analogues, indicates the aryl amides and esters as well as the alkyl esters as interesting scaffolds to design and develop novel anticancer agents. 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
- Damio, Mariana C. F. C. B.,Pasqualoto, Kerly F. M.,Ferreira, Adilson K.,Teixeira, Sarah F.,Azevedo, Ricardo A.,Barbuto, Jos A. M.,Palace-Berl, Fanny,Franchi-Junior, Gilberto C.,Nowill, Alexre E.,Tavares, Maurcio T.,Parise-Filho, Roberto
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p. 885 - 895
(2015/02/19)
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- Design and synthesis of conformationally restricted capsaicin analogues based in the 1, 3, 4-thiadiazoleheterocycle reveal a novel family of transient receptor potential vanilloid 1 (TRPV1) antagonists
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4-hydroxy-3-methoxybenzaldehyde was used as starting material to obtain a number of 1, 3, 4-thiadiazole alkylamide derivatives. The pharmacological properties of these conformationally restricted capsaicin analogues were evaluated on HEK-293T cells transiently expressing TRPV1 receptor. By means of a highthroughput calcium imaging assay we find that 1, 3, 4-thiadiazoles (compounds 8-15) act as potent antagonists of the capsaicin receptor, inhibiting both, the capsaicin- and temperature-dependent activation. Docking studies suggested a different binding orientation on the vanilloid binding site when compared with capsaicin analogues, such as 5-iodononivamide. Overall, our studies suggest that 1, 3, 4-thiadiazoles interact with capsaicin 's binding region of the receptor, although using a different set of interactions within the vanilloid binding pocket.
- Rebolledo, Carolyne Lespay,Sotelo-Hitschfeld, Pamela,Brauchi, Sebastián,Olavarría, Miguel Zárraga
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p. 193 - 203
(2013/10/01)
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- Synthesis and antimicrobial activity of the essential oil compounds (E)- and (Z)-3-hexenyl nonanoate and two analogues
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Numerous studies and reviews on the subject matter of compounds isolated from plants have demonstrated that essential oil compounds display antimicrobial activity1-7. Of particular interest to this work is a study 8 where it was found that (Z)-3-hexenyl nonanoate 1a (Figure 1) was a major essential oil component (16 %) from Heteropyxis natalensis, a deciduous tree, from the family Heteropyxidaceae, having strongly aromatic foliage and being specific to the geographical location of Lagalametse in the Waterberg (Northern Province, South Africa). In addition, the (E)-isomer 1b has also been observed in plants, albeit in much lower amounts - see for instance the 0.2 % of this compound isolated from Cinnamomum tamala (Ham.) Nees & Eberm. 9 The authors of the South African study on Heteropyxis natalensis postulated that the particular (Z)-compound could be responsible for the overall antimicrobial properties of the essential oil. This hypothesis was based on a geographical variation study, whereby differences of antimicrobial activity were observed between varied regions. The most active (mean MIC value of 2.1 mg mL-1 against five test pathogens) of the Heteropyxis natalensis oil was evident where the major constituent comprised of (Z)-3-hexenyl nonanoate 1a. This compound was not present in any of the other geographical samples which had poorer activity (mean MIC value of between 4.0-7.4 mg mL-1 against the five test pathogens)8. Of interest is that compound 1a which has been associated with food additives; however, little else is known concerning the biological properties of these particular class of compounds. It was thus decided to synthesize compounds 1a and 1b, as well as two structural analogues 1c and 1d and test them for their putative antimicrobial efficacy.
- Chakravorty, Santanu,Rayner, Matthew K.,De Koning, Charles B.,Van Vuuren, Sandy F.,Van Otterlo, Willem A. L.
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p. 202 - 205
(2013/01/15)
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- Synthesis, insecticidal evaluation of novel 1,3,4-thiadiazole chrysanthemamide derivatives formed by an EDCI/HOBt condensation
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A series of novel pesticides with two components derived from a 1,3,4-thiadiazole and chrysanthemic acid were synthesised via an EDCI/HOBt condensation. These 1,3,4-thiadiazole chrysanthemamides were identified by IR, 1H NMR and elemental analyses. Their insecticidal activity was also evaluated.
- Yu, Peng,Hu, Jun,Zhou, Tao-Yu,Wang, Peng,Xu, Yan-Hua
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experimental part
p. 703 - 706
(2012/03/10)
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- Synthesis and insecticidal activities of 1,3,5-trisubstituted-1,3,5- hexahydrotriazine-2-N-nitroimines
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A new series of 1,3,5-trisubstituted-1,3,5-hexahydrotriazine-2-N- nitroimines (3a-3j) were designed and synthesized as novel neonicotinoid analogues, and their structures were characterized by 1H NMR, IR, elemental analysis and MS. The preliminary bioassay tests showed that most of the target compounds had good insecticidal activities against Nilaparvata lugens as well as Aphis medicaginis at 500 mg/L, while compound 3i had 100% mortality against Nilaparvata lugens at 20 mg/L.
- Xue, Sijia,Ma, Xubo,Bu, Hongfei,Liu, Li,Xu, Xiao
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scheme or table
p. 2153 - 2156
(2012/03/26)
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- Novel amides and esters prodrugs of olmesartan: Synthesis, bioconversion, and pharmacokinetic evaluation
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Synthesis of novel amides and esters prodrugs of olmesartan is described. Their in vitro stability in rat plasma was tested. The results showed that the ester derivative IIa with n-octyl substituted dioxolone moiety was rapidly converted into olmesartan within 30 min. The pharmacokinetic parameters of IIa were studied and compared with those of olmesartan medoxomil. Compound IIa is proposed to be a promising prodrug of olmesartan.
- Park, Jin-Hun,Chang, Jeong-Soo,El-Gamal, Mohammed I.,Choi, Won-Kyoung,Lee, Woong San,Chung, Hye Jin,Kim, Hyun-Il,Cho, Young-Jin,Lee, Bong Sang,Jeon, Hong-Ryeol,Lee, Yong Sup,Choi, Young Wook,Lee, Jaehwi,Oh, Chang-Hyun
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scheme or table
p. 5895 - 5899
(2010/11/18)
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- 3-Substituted isocoumarins as thymidine phosphorylase inhibitors
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3-Substituted isocoumarins 1-19 were synthesized and evaluated for their thymidine phosphorylase inhibitory activity. Eight (8) compounds exhibited a varying degree of inhibitory activity towards thymidine phosphorylase from E. coli with IC50 values between 61- 402 μM. The activities were compared with the standard 7-deazaxanthine (IC50 = 39.28 ± 0.76 μM).
- Khan, Khalid Mohammed,Ahmed, Sumbul,Hussain, Sajjad,Ambreen, Nida,Perveen, Shahnaz,Choudhary, M. Iqbal
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body text
p. 265 - 268
(2011/03/18)
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- Cl3CCONH2/PPh3: A versatile reagent for synthesis of esters
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Cl3CCONH2/PPh3 was a versatile reagent to convert carboxylic acids into their corresponding acid chlorides. This intermediate was clearly confirmed by spectroscopic methods (IR, 1H, 13C NMR). This one-pot reaction of in situ acid chloride generated with various alcohols successfully furnished the corresponding esters in moderate to excellent yields. Copyright ? Taylor & Francis Group, LLC.
- Chantarasriwong, Oraphin,Jang, Doo Ok,Chavasiri, Warinthorn
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experimental part
p. 2845 - 2856
(2009/04/11)
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- Chili pepper fruits: Presumed precursors of fatty acids characteristic for capsaicinoids
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Capsaicin is a molecule unique to fruits from the genus Capsicum. It is responsible for the pungent sensation and displays valuable pharmacological properties. Despite the fruits' economic importance and decades of research, the regulation of the content of capsaicinoids in individual fruits is not completely elucidated, and no agricultural cultivation of chili of defined pungency is assured. Precursor candidates of the fatty acid moiety of the capsaicinoids, especially for the unique 8-methyl-trans-6-nonenoic acid, were examined. Thioesters, acyl-ACP and acyl-CoA, were isolated from the placenta of Capsicum fruits by means of DEAE-Sepharose chromatography, selectively converted to the corresponding N-butylamides, and analyzed by GC-MS. Fatty acid moieties characteristic for capsaicinoids were identified. In two different varieties (Capsicum chinense var. Habanero orange and Capsicum annuum var. Jalapeno) it was shown that the fatty acid pattern corresponds to the distribution pattern of the capsaicinoids formed up to this time. The acyl-thioester fractions contained already the 8-methyl-trans-6-nonenoic acid.
- Thiele, Roland,Mueller-Seitz, Erika,Petz, Michael
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experimental part
p. 4219 - 4224
(2010/03/31)
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- Synthesis and transdermal permeation-enhancing activity of carbonate and carbamate analogs of Transkarbam 12
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Transkarbam 12 (5-(dodecyloxycarbonyl)pentylammonium-5-(dodecyloxycarbonyl)pentylcarbamate, T12) is a highly effective skin permeation enhancer. In this study, ester groups in the molecule of T12 were replaced by carbonate and carbamate ones, respectively. The in vitro permeation-enhancing activities were evaluated using porcine skin and compared with those of T12 and previously prepared series of amide, ketone, and alkyl analogs. According to the activities and behavior of the compounds in donor samples, ester group is essential for the activity of T12; its replacement not only decreases the enhancing potency, but is likely to change the mechanism of action.
- Holas, Tomas,Vavrova, Katerina,Sima, Martin,Klimentova, Jana,Hrabalek, Alexandr
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p. 7671 - 7680
(2007/10/03)
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- New esters of vanillin and vanillal with some alkane- and arenecarboxylic acids
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Previously unknown esters were synthesized by the reaction of vanillin and vanillal with carboxylic acid chlorides. Pleiades Publishing, Inc., 2006.
- Dikusar
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p. 1035 - 1037
(2008/02/05)
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- Synthesis of esters of D, L-, D(+)-, and L(-)-camphor oximes: Structure-odor correlation
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Esters of D,L-, D(+)-, and L(-)-camphor oximes were synthesized, and the correlation between their structure and odor was examined.
- Dikusar,Zhukovskaya,Vyglazov
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p. 1982 - 1985
(2008/02/08)
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- Inhibitors of fatty acid amide hydrolase
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Improved competitive inhibitors of FAAH employ an α-keto heterocyclic pharmacophore and a binding subunit having a ?-unsaturation. The α-keto heterocyclic pharmacophore and a binding subunit are attached to one another, preferably by a hydrocarbon chain. The improvement lies in the use of a heterocyclic pharmacophore selected from oxazoles, oxadiazoles, thiazoles, and thiadiazoles that have alkyl or aryl substituents at their 4 and/or 5 positions. The improved competitive inhibitors of FAAH display enhanced activity over conventional competitive inhibitors of FAAH.
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Page/Page column 9
(2008/06/13)
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- Discovery of a potent, selective, and efficacious class of reversible α-ketoheterocycle inhibitors of fatty acid amide hydrolase effective as analgesics
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Fatty acid amide hydrolase (FAAH) degrades neuromodulating fatty acid amides including anandamide (endogenous cannabinoid agonist) and oleamide (sleep-inducing lipid) at their sites of action and is intimately involved in their regulation. Herein we report the discovery of a potent, selective, and efficacious class of reversible FAAH inhibitors that produce analgesia in animal models validating a new therapeutic target for pain intervention. Key to the useful inhibitor discovery was the routine implementation of a proteomics-wide selectivity screen against the serine hydrolase superfamily ensuring selectivity for FAAH coupled with systematic in vivo examinations of candidate inhibitors.
- Boger, Dale L.,Miyauchi, Hiroshi,Du, Wu,Hardouin, Christophe,Fecik, Robert A.,Cheng, Heng,Hwang, Inkyu,Hedrick, Michael P.,Leung, Donmienne,Acevedo, Orlando,Guimar?es, Cristiano R. W.,Jorgensen, William L.,Cravatt, Benjamin F.
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p. 1849 - 1856
(2007/10/03)
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- Method for purifying acid chlorides
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Process for the purification of carbonyl chlorides which have been prepared by reacting carboxylic acids with phosgene or thionyl chloride in the presence of a catalyst adduct, in which the carbonyl chlorides are treated with a hydrohalide of carboxamides of the formula (I) in which R1is hydrogen or C1- to C3-alkyl; R2and R3independently of one another are C1- to C4-alkyl, or R2and R3together are a C4- or C5-alkylene chain, and the carbonyl chloride purified in this way is isolated by separation off from the carboxamide hydrohalide phase.
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Page column 12
(2008/06/13)
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- Method for producing acid chlorides
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The invention relates to a method for producing acid chlorides by converting carboxylic acids with carbon oxychlorides or thionyl chloride in the presence of a catalyst adduct of an N,N-disubstituted formamide of general formula (I) and carbon oxychloride or thionyl chloride. In the formula, R1and R2, independently from one another, mean C1- to C4-alkyl or R1and R2together mean a C4- or C5-alkylene chain. According to the inventive method, hydrogen chloride is added during and/or after the conversion.
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Page column 10-11
(2008/06/13)
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- MERCAPTOKETONES AND MERCAPTOALCOHOLS AND A PROCESS FOR THEIR PREPARATION
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This invention relates to matrix metalloproteinase (MMP) inhibiting compounds of the formula: STR1 where R 1 is C 1-C 12 alkyl, straight or branched and optionally substituted by halogen, hydroxy, C. sub.1-C 6 alkoxy, amino, carboxyl, C 1-C. sub.6 alkoxycarbonyl, carboxamido, nitrile, mono-or di-(C 1-C 6) alkylamino, thio, C 1-C 6 alkylthio, aryl,--Oaryl or--OCH. sub. 2 aryl where aryl is optionally substituted with C 1-C 6 alkyl, C 1-C 6 alkoxy, carboxy, halogen, cyano, nitro, carboxamido, or hydroxy; and C 1-C. sub.6 alkanesulfonyloxy. R 2 is α-OH or β-OH and R 6 is H or R. sup.2 and R 6 together are carbonyl; the chemical intermediates; and processes for the preparation of these compounds and the intermediates thereto. Matrix metalloproteinases (MMP) are a family of zinc-containing calcium dependent proteinases, including stromelysins, collagenases, and gelatinases. These MMP enzymes are capable of degrading the proteinaceous components of connective tissue and appear to be involved in tissue remodeling, i.e., wound healing and connective tissue turnover. Unexpectedly, the mercaptoalcohols with the S-configuration at the hydroxyl-bearing carbon have been found to be at least 4 times more potent than the analogous (R)-alcohols both in vitro and in vivo in inhibiting the MMP enzyme.
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- Mercaptoketones and mercaptoalcohols, a process for their preparation and their use as inhibitors of matrix metalloproteinases
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This invention relates to matrix metalloproteinase (MMP) inhibiting compounds of the formula: where R1is C1-C12alkyl, straight or branched and optionally substituted by halogen, hydroxy, C1-C6alkoxy, amino, carboxyl, C1-C6alkoxycarbonyl, carboxamido, nitrile, mono- or di-(C1-C6)alkylamino, thio, C1-C6alkylthio, aryl, -Oaryl or -OCH2aryl where aryl is optionally substituted with C1-C6alkyl, C1-C6alkoxy, carboxy, halogen, cyano, nitro, carboxamido, or hydroxy; and C1-C6alkanesulfonyloxy. R2is α-OH or β-OH and R6is H or R2and R6together are carbonyl; the chemical intermediates; and processes for the preparation of these compounds and the intermediates thereto. Matrix metalloproteinases (MMP) are a family of zinc-containing calcium dependent proteinases, including stromelysins, collagenases, and gelatinases. These MMP enzymes are capable of degrading the proteinaceous components of connective tissue and appear to be involved in tissue remodeling, i.e., wound healing and connective tissue turnover. Unexpectedly, the mercaptoalcohols with the S-configuration at the hydroxyl-bearing carbon have been found to be at least 4 times more potent than the analogous (R)-alcohols both in vitroand in vivoin inhibiting the MMP enzyme..
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- A convenient synthesis of pheromones (Z)-7-Nonadecen-11-one, (Z)-7-eicosen-11-one and γ-dodecanolide
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Friedel-Crafts acylation of acetylene with acid chloride (ROCl, R = C8, C9) provides a key synthon, β-chlorovinyl ketone (Ia,b) that on cyanation, ketalization followed by hydrogenation with Pd/C and DIBAL-H reduction furnishes γ-ketoaldehyde (Va,b).Wittig olefination of V(a,b) with n-heptyltriphenylphosphonium bromide, provides stereoselectively (Z)-7-nonadecen-11-one (1) and (Z)-7-eicosen-11-one (2), respectively.The β-ketovinyl cyanide IIa on hydrogenation and reduction with baker's yeast gives (S)-(-)-4-hydroxydodecanonitrile (VII), which on alkaline hydrolysisand subsequent acidification with HCl furnishes (R)-(+)-γ-n-dodecanolactone (3).
- Bhalerao, U T,Devalla, Sridhar,Rao, Vittal
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p. 266 - 268
(2007/10/02)
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- Vanilloids. 1. Analogs of Capsaicin with Antinociceptive and Antiinflammatory Activity
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As part of a program to establish structure-activity relationships for vanilloids, analogs of the pungent principle capsaicin, the alkyl chain portion the parent structure (and related compounds derived from homovanillic acid) was varied.In antinociceptive and antiinflammatory assays (rat and mouse hot plate and croton oil-inflamed mouse ear), compounds with widely varying alkyl chain structures were active.Short-chain compounds were active by systemic administration in the assays mentioned above but they retained the high pungency and acute toxicity characteristic of capsaicin.In contrast, the long chain cis-unsaturates, NE-19550 (vanillyloleamide) and NE-28345 (oleylhomovanillamide), were orally active, less pungent, and less acutely toxic than capsaicin.The potential of these compounds as antiinflammatory/analgesic agents is discussed in light of recent data on the mechanism of action of vanilloids on sensory nerve fibers.
- Janusz, John M.,Buckwalter, Brian L.,Young, Patricia A.,LaHann, Thomas R.,Farmer, Ralph W.,et al.
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p. 2595 - 2604
(2007/10/02)
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- REACTION OF PHOSPHORUS TRICHLORIDE WITH CARBOXYLIC ACIDS
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The reaction of phosphorus trichloride with a number of monobasic carboxylic acids has been studied and the optimum ratio of reactants for the yield of acid chlorides has been established.Based on analysis and the data from 31P NMR spectroscopy of the phosphorus-containing products from this reaction it is shown that at 40-50 deg C a mixture of P-H acids having a predominant content of pyrophosphorous acid is formed.
- Valitova, L. A.,Popova, E. V.,Ibragimov, Sh. N.,Ivanov, B. E.
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p. 366 - 370
(2007/10/02)
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- The Effect of Halogen Substitution on the Side Chains of Discotic Liquid Crystals
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The thermal phase behavior of the hexa(ester)s of benzene-, 1,2,3,4,5,6-all trans cyclohexane- and 2,3,6,7,10,11-triphenylene-hexa(alcohol)s with ω-bromine substituted side chains is described.Terminal bromine substitution on the side chains of cyclohexane hexaesters gives a series of discogens for which the clearing temperature decreases monotonically as side chain length increases, ΔTM-I = -133 deg C for the span of side chain lengths C5 to C11.In contrast, the parent discogens exhibit only a small decrease of TM-I as the side chain increases in length from C6 to C12, ΔTM-I = -23 deg C.This effect is discussed in terms of dipole-dipole interactions between the side chain termini and between the side chains and the disc-like core.
- Lillya, C. P.,Collard, D. M.
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p. 201 - 207
(2007/10/02)
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- Monitored Aminolysis of 3-Acyl-1,3-thiazolidine-2-thiones: Synthesis of Amides and Amide Alkaloids
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A functional heterocycle, 3-acyl-1,3-thiazolidine-2-thione has been shown to be effective as an acylating reagent for the amino group.ATT (1) was readily prepared by several methods, and reacted with various amino compounds in CHCl3, CH2Cl2, THF, EtOH, THF-H2O, or sulfolane to afford the corresponding amides, 2a-w and 3-10 in very high yields within a short time.This reagent exhibits high chemo-selectivity.Its reaction with the diamines 13 and 15 and the triamine 29, which include a primary amino group(s) and a secondary amino group, gave the products acylated only at the primary amino group(s), 14, 16, and 30, respectively, in high yields.Aminoalcohols and aminophenols were chemoselectively converted into acylaminoalcohols and acylaminophenols, respectively, by ATT (1).By utilizing this method, several amide alkaloids (26, 28, 30, and 34) were efficiently synthesized.This new aminolysis can be monitored by the disappearance of the yellow color of the starting materials, ATT (1); it is remarkably characteristic of this reaction. Keywords - monitored aminolysis; 3-acyl-1,3-thiazolidine-2-thione; high chemo-selectivity; amide synthesis; fagaramide; dolicotheline; spermidine; maytenine; N-ferulyltryptamine
- Nagao, Yoshimitsu,Seno, Kaoru,Kawabata, Kohji,Miyasaka, Tadao,Takao, Sachiko,Fujita, Eiichi
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p. 2687 - 2699
(2007/10/02)
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