- Unexpected stereoselective exchange of straight-chain fatty acyl-CoA α-protons by human α-methylacyl-CoA racemase 1A (P504S)
-
α-Methylacyl-CoA racemase (AMACR; P504S) catalysed exchange of straight-chain fatty acyl-CoA α-protons. One α-proton was removed in each catalytic cycle, with the pro-S proton preferred. This reaction was most efficient for straight-chain substrates with longer side-chains. 2-Methyldecanoyl-CoA underwent α-proton exchange 3× more efficiently (as judged by Kcat/Km) than decanoyl-CoA.
- Sattar, Fouzia A.,Darley, Daniel J.,Politano, Francesco,Woodman, Timothy J.,Threadgill, Michael D.,Lloyd, Matthew D.
-
-
Read Online
- "Meta elimination," a diagnostic fragmentation in mass spectrometry
-
The diagnostic value of the "ortho effect" for unknown identification by mass spectrometry is well known. Here, we report the existence of a novel "meta effect," which adds to the repertoire of useful mass spectrometric fragmentation mechanisms. For example, the meta-specific elimination pathway described in this report enables unequivocal identification of meta isomers from ortho and para isomers of carboxyanilides. The reaction follows a specific path to eliminate a molecule of meta-benzyne, from the anion produced after the initial decarboxylation of the precursor. Consequently, in the CID spectra of carboxyanilides, a peak for the (R-CO-NH)- anion is observed only for the meta isomers. For example, the peaks observed at m/z 58, 86, 120, 128, and 170 from acetamido-, butamido-, benzamido, heptamido-, and decanamido-benzoates, respectively, were specific only to the spectra of meta isomers.
- Attygalle, Athula B.,Nishshanka, Upul,Weisbecker, Carl S.
-
-
Read Online
- Synthesis, characterization, and properties of copolyanhydrides based on 2-octylsuccinic acid and sebacic acid
-
2-Octylsuccinic acid and its copolyanhydrides with sebacic acid have been synthesized by melt polycondensation, and were characterized by Fourier transform infrared spectroscopy, 1H NMR, gel permeation chromatography, differential scanning calorimetry, and thermal gravimetric analysis. In vitro studies showed that all copolymers are degradable in phosphate buffer at 37°C. The release profiles of the hydrophilic model drug ciprofloxacin hydrochloride follow first-order release kinetics. CSIRO 2008.
- Hamdan, Yousef M.,Fu, Shitao,Jiang, Xiangmei,Cheng, Yinhua,Huang, Kaixun,Yu, Kaichao
-
-
Read Online
- Ferroelectric liquid crystals induced by atropisomeric dopants: Dependence of the polarization power on the core structure of the smectic C host
-
A series of 11 chiral dopants with an atropisomeric core derived from 4,4′-dihydroxy-2,2′,6,6′-tetramethyl-3,3′- dinitrobiphenyl were synthesized in optically pure form. These compounds were doped into five different smectic C (SC) liquid crystal hosts to induce a ferroelectric SC* liquid crystal phase, and the reduced polarization Po was measured as a function of the dopant mole fraction xd over the range 0.005 d ≤ 0.05. The polarization power δp was found to strongly depend on the core structure of the SC host. For example, the dopant (+)-2,2′,6,6′-tetramethyl-3,3′-dinitro-4,4′-bis[(4- octyloxybenzoyl)oxy]biphenyl gave δp values of 2 in a phenyl benzoate SC host and 1738 nC/cm2 in a phenylpyrimidine SC host; the latter is one of the highest polarization power values reported thus far in the literature. In the phenylpyrimidine SC host, the polarization power was found to depend on the length of the dopant side chains and on the position of the atropisomeric core with respect to those of the surrounding SC host molecules, on the time average. The polarization power followed a trend opposite to that followed by the SC* helical pitch. Analysis of these results suggests that chirality transfer from the atropisomeric core of the dopant to those of the Sc host molecules plays a key role in amplifying the polarization induced in the phenylpyrimidine host. It is likely that such intercore chirality transfer results in an asymmetric distortion of the SC* lattice, which in turn, further increases the conformational asymmetry of the chiral dopant by virtue of increased diastereomeric bias between the SC* lattice and the chiral conformations of the dopant.
- Vizitiu, Despina,Lazar, Carmen,Halden, Brian J.,Lemieux, Robert P.
-
-
Read Online
- The effect of vicinal di-halo substituents on the organogelling properties of aromatic supramolecular gelators and their application as soft templates
-
A pronounced effect of vicinal dihalogen substituents on the gelling properties of aromatic low molecular weight organogelators is reported. A new family of N,N′-(4,5-dihalogen-1,2-phenylene)dialkylamides with fluorine, chlorine, bromine and iodine was designed and synthesized. A systematic investigation of their organogelling ability, thermic stability, mechanical properties and self-assembled structure was performed to elucidate the effect that the vicinal di-halo substituents have on the organogels. It was found that the presence of two halogen atoms (X) has a determinant effect as the brominated compounds are generally the most efficient organogelators. In hydrocarbons, the gelling ability increased from fluorine to iodine following the halogen bond donor ability trend. SAXS results were in agreement with a fibrillar self-assembly where the halogens are located at the surface of the fibers. Multiple cooperative interactions are involved in the self-assembly of the gels: π-π stacking, hydrogen bonds and X?X contacts. Thus, this work provides a new strategy for the design of new gelators or to improve the efficiency of known organogelators by introducing two vicinal halogen substituents into the aromatic rings. An ethanolic gel was also successfully used as a template to prepare silica and titania nanotubes. Hence, such organogels are promising materials for future research and development.
- Busch, Verónica M.,Di Chenna, Pablo H.,Di Salvo, Florencia,Giovanetti, Lisandro,Japas, M. Laura,MacCormack, Andrea S.
-
-
Read Online
- Synthesis and transdermal permeation-enhancing activity of carbonate and carbamate analogs of Transkarbam 12
-
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
-
-
Read Online
- Selective reduction of barbituric acids using SmI2/H 2O: Synthesis, reactivity, and structural analysis of tetrahedral adducts
-
Making a mark: Since the 1864 landmark discovery by Adolf von Baeyer, barbituric acids have played a prominent role in organic synthesis. Herein, the first chemoselective monoreduction of barbituric acids to the corresponding hemiaminals is described. The method delivers mono- and bicyclic hemiaminal products by a general single-electron-transfer polarity reversal mechanism. Re-use of this article is permitted in accordance with the Terms and Conditions set out at http://angewandte.org/open.
- Szostak, Michal,Sautier, Brice,Spain, Malcolm,Behlendorf, Maike,Procter, David J.
-
-
Read Online
- 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)
-
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.
-
-
Read Online
- L-ascorbyl 6-palmitate as lead compound targeting SphK1: an in silico and in vitro investigation
-
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
-
-
Read Online
- Benzimidazole tethered thioureas as a new entry to elastase inhibition and free radical scavenging: Synthesis, molecular docking, and enzyme inhibitory kinetics
-
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
-
-
Read Online
- Synthesis, calorimetric studies, and crystal structures of N, O-diacylethanolamines with matched chains
-
Recent studies show that N-, O -diacylethanolamines (DAEs) can be derived by the O -acylation of N-acylethanolamines (NAEs) under physiological conditions. Because the content of NAEs in a variety of organisms increases in response to stress, it is likely that DAEs may also be present in biomembranes. In view of this, a homologous series of DAEs with matched acyl chains (n = 10-20) have been synthesized and characterized. Transition enthalpies and entropies obtained from differential scanning calorimetry show that dry DAEs with even and odd acyl chains independently exhibit linear dependence on the chainlength. Linear least-squares analyses yielded incremental values contributed by each methylene group to the transition enthalpy and entropy and the corresponding end contributions. N-, O-Didecanoylethanolamine (DDEA), N-, O-dilauroylethanolamine (DLEA), and N-, O-dimyristoylethanolamine (DMEA) crystallized in the orthorhombic space group Pbc21 with four symmetry-related molecules in the unit cell. Single-crystal X-ray diffraction studies show that DDEA, DLEA, and DMEA are isostructural and adopt an L-shaped structure with the N-acyl chain and the central ethanolamine moiety being essentially identical to the structure of N-acylethanolamines, whereas the O-acyl chain is linear with all-trans conformation. In all three DAEs, the lipid molecules are organized in a bilayer fashion wherein the N-acyl and O-acyl chains from adjacent layers oppose each other. Copyright
- Kamlekar, Ravi Kanth,Tarafdar, Pradip K.,Swamy, Musti J.
-
-
Read Online
- Conformation, and Charge Tunneling through Molecules in SAMs
-
This paper demonstrates that the molecular conformation (in addition to the composition and structure) of molecules making up self-assembled monolayers (SAMs) influences the rates of charge tunneling (CT) through them, in molecular junctions of the form AuTS/S(CH2)2CONR1R2//Ga2O3/EGaIn, where R1 and R2 are alkyl chains of different length. The lengths of chains R1 and R2 were selected to influence the conformations and conformational homogeneity of the molecules in the monolayer. The conformations of the molecules influence the thickness of the monolayer (i.e. tunneling barrier width) and their rectification ratios at ±1.0 V. When R1 = H, the molecules are well ordered and exist predominantly in trans-extended conformations. When R1 is an alkyl group (e.g., R1 H), however, their conformations can no longer be all-trans-extended, and the molecules adopt more gauche dihedral angles. This change in the type of conformation decreases the conformational order and influences the rates of tunneling. When R1 = R2, the rates of CT decrease (up to 6.3×), relative to rates of CT observed through SAMs having the same total chain lengths, or thicknesses, when R1 = H. When R1 H R2, there is a weaker correlation (relative to that when R1 = H or R1 = R2) between current density and chain length or monolayer thickness, and in some cases the rates of CT through SAMs made from molecules with different R2 groups are different, even when the thicknesses of the SAMs (as determined by XPS) are the same. These results indicate that the thickness of a monolayer composed of insulating, amide-containing alkanethiols does not solely determine the rate of CT, and rates of charge tunneling are influenced by the conformation of the molecules making up the junction.
- Belding, Lee,Root, Samuel E.,Li, Yuan,Park, Junwoo,Baghbanzadeh, Mostafa,Rojas, Edwin,Pieters, Priscilla F.,Yoon, Hyo Jae,Whitesides, George M.
-
supporting information
p. 3481 - 3493
(2021/03/08)
-
- Synthesis, computational studies and enzyme inhibitory kinetics of benzothiazole-linked thioureas as mushroom tyrosinase inhibitors
-
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.
-
p. 7035 - 7043
(2020/08/12)
-
- Neutrophil-Selective Fluorescent Probe Development through Metabolism-Oriented Live-Cell Distinction
-
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
-
supporting information
p. 23743 - 23749
(2021/10/14)
-
- Structure-Activity Relationship Study of Majusculamides A and B and Their Analogues on Osteogenic Activity
-
We discovered that majusculamide A (1) and majusculamide B (2), isolated from a marine cyanobacterium collected in Okinawa, induced osteoblast differentiation in MC3T3-E1 cells. Although majusculamide A (1) has a different configuration only at the C-19 stereocenter, bearing a methyl group, compared to majusculamide B (2), the effect of 1 was stronger than that of 2. We synthesized some analogues of the majusculamides (3-15) and evaluated osteogenic activities of these analogues. The structure-activity relationship study of majusculamide analogues suggested that the number of methyls and configuration at C-19 and the nature of the substituent at C-20 of majusculamide A (1) may be important for the osteoblast differentiation-inducing effect of 1.
- Nakajima, Daisuke,Natsume, Noriyuki,Ozaki, Kaori,Teruya, Toshiaki,Yokoshima, Satoshi
-
supporting information
p. 2477 - 2482
(2020/10/02)
-
- PYRROLE DERIVATIVES AS ACC INHIBITORS
-
Novel pyrrole derivatives of Formula (I) are disclosed; as well as process for their preparation, pharmaceutical compositions comprising them and their use in therapy as inhibitors of Acetyl- CoA carboxylase (ACC).
- -
-
Page/Page column 48
(2019/07/19)
-
- Synthesis and anticancer evaluation of new lipophilic 1,2,4 and 1,3,4-oxadiazoles
-
A series of1,2,4- and 1,3,4-oxadiazole derivatives were synthesized and evaluated for their anticancer activity. Halogenated 1,2,4-oxadiazoles were obtained from benzonitrile and coupled either lipophilic amines or with aminoalcohols. Lipophilic 1,3,4-oxadiazole derivatives were obtained through the Mannich reactions between 5-(aryl)-1,3,4-oxadiazole-2-thiol and alkylated or acylated amines. The in vitro cytotoxic effects were evaluated against 4T1– mammary carcinoma and CT26 – colon cancer cells. The best results were obtained for the 1,3,4-oxadiazole coupled to alkylated piperazine with 10–14 carbon chain moiety, with IC50 values ranging from 1.6 to 3.55μΜ for the 4T1 cell line, and from 1.6 to 3.9 μM for the CT26.WT cell line, and selectivity index up to 19. The most potent compounds were investigated with AnnexinV and PI staining as indicative of apoptosis induction.
- Caneschi, Wiliam,Enes, Karine Braga,Carvalho de Mendon?a, Camille,de Souza Fernandes, Fábio,Miguel, Fabio Balbino,da Silva Martins, Jefferson,Le Hyaric, Mireille,Pinho, Roberto Rosas,Duarte, Lucas Mattos,Leal de Oliveira, Marcone Augusto,Dos Santos, Hélio F.,Paz Lopes, Miriam Teresa,Dittz, Dalton,Silva, Heveline,Costa Couri, Mara Rubia
-
-
- Cinnamyl alcohol fatty acid ester derivative and application and preparation method thereof
-
The invention relates to a derivative and an application and a preparation method thereof, in particular to a cinnamyl alcohol fatty acid ester derivative and an application and a preparation method thereof. As application of a percutaneous absorption penetration enhancer, a percutaneous administration preparation is prepared, so that the percutaneous absorption of a drug is improved, and the cumulative penetration amount of the drug is increased. The cinnamyl alcohol fatty acid ester derivative is prepared into fatty acyl chloride, and the fatty acyl chloride reacts with cinnamyl alcohol to obtain the cinnamyl alcohol fatty acid ester derivative. The compound can be applied to the percutaneous administration preparation to enhance the drug permeability, can further be used as perfume to cover up the bad smell of the preparation, and has wide potential application prospects.
- -
-
Paragraph 0050; 0051
(2019/05/08)
-
- Preparation method of 2, 6-dimethylaniline long-chain compound
-
The invention discloses a preparation method of a 2, 6-dimethylaniline long-chain compound. The method comprises S1, mixing a compound II and a compound III with a first solvent, and adding in a firstbase catalyst for reaction at 0-80 DEG C to obtain a compound IV; S2, uniformly mixing the compound IV prepared in S1, a compound V and a second solvent for mixed reaction at 70-120 DEG C, washing reaction products through ethyl acetate, and filtering out precipitates, namely a compound VI; S3, mixing the compound VI prepared in S2, a second base catalyst, a reactant A, alcohols and a third solvent for mixed reaction at 30-80 DEG C to obtain a compound I, wherein the reactant A is an acyl chloride or ester compound. According to the preparation method of the 2, 6-dimethylaniline long-chain compound, the applied raw materials are all common chemical materials and accordingly are wide in resource and low in prices, products of every reaction save complicated column chromatography and can berecrystallized into high-purity products, so that the preparation method of the 2, 6-dimethylaniline long-chain compound has an industrial scaled synthesis prospect.
- -
-
Paragraph 0023; 0032-0036
(2019/04/17)
-
- An efficient synthesis of benzothiazole using tetrabromomethane as a halogen bond donor catalyst
-
An efficient and mild protocol has been developed for the synthesis of 2-substituted benzothiazole under solvent- and metal-free conditions using CBr4 as the catalyst. This process involves the activation of a thioamide through halogen bond formation between the sulphur atom of the thioamide and bromine atom of the CBr4 molecule. The presence of halogen-bonding interaction between N-methylthioamides and tetrabromomethane has been demonstrated with several control experiments, spectroscopic analysis and density functional theory (DFT). This methodology has a wide substrate scope for the synthesis of both 2-alkyl and 2-aryl substituted benzothiazoles.
- Kazi, Imran,Sekar, Govindasamy
-
p. 9743 - 9756
(2019/12/02)
-
- COMPOUNDS WITH HIV MATURATION INHIBITORY ACTIVITY
-
The present invention relates to compound of Formula I or a pharmaceutically acceptable salt thereof (Formula I) wherein R1 is Formula (AA) or Formula (BB) where the squiggly line indicates the point of attachment to the rest of the molecule; R2 is F or Formula (CC) where the squiggly line indicates the point of attachment to the rest of the molecule; R3 is H or CH3; Z is O or is absent; and R4 is -OC1-3alkyl, C1-30alkyl, or -N(CH3)2.
- -
-
Page/Page column 10
(2019/11/12)
-
- 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
-
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
-
p. 687 - 693
(2018/07/29)
-
- Discovery of long-chain salicylketoxime derivatives as monoacylglycerol lipase (MAGL) inhibitors
-
Monoacylglycerol lipase (MAGL) is the enzyme hydrolyzing the endocannabinoid 2-arachidonoylglycerol (2-AG) to free arachidonic acid and glycerol. Therefore, MAGL is implicated in many physiological processes involving the regulation of the endocannabinoid system and eicosanoid network. MAGL inhibition represents a potential therapeutic target for many diseases, including cancer. Nowadays, most MAGL inhibitors inhibit this enzyme by an irreversible mechanism of action, potentially leading to unwanted side effects from chronic treatment. Herein, we report the discovery of long-chain salicylketoxime derivatives as potent and reversible MAGL inhibitors. The compounds herein described are characterized by a good target selectivity for MAGL and by antiproliferative activities against a series of cancer cell lines. Finally, modeling studies suggest a reasonable hypothetical binding mode for this class of compounds.
- Bononi, Giulia,Granchi, Carlotta,Lapillo, Margherita,Giannotti, Massimiliano,Nieri, Daniela,Fortunato, Serena,Boustani, Maguie El,Caligiuri, Isabella,Poli, Giulio,Carlson, Kathryn E.,Kim, Sung Hoon,Macchia, Marco,Martinelli, Adriano,Rizzolio, Flavio,Chicca, Andrea,Katzenellenbogen, John A.,Minutolo, Filippo,Tuccinardi, Tiziano
-
p. 817 - 836
(2018/08/24)
-
- Visible-Light-Mediated Iminyl Radical Generation from Benzyl Oxime Ether: Synthesis of Pyrroline via Hydroimination Cyclization
-
The treatment of an O-(4-methoxybenzyl) oxime ether bearing an olefin substituent and 1-chloroanthraquinone (1-Cl-AQN) catalyst in 2-butanone under visible-light irradiation affords pyrroline via an iminyl radical intramolecular hydroimination. Mechanistic studies indicate that iminyl radical generation mainly proceeds by hydrogen abstraction of the photocatalyst from the benzyl position of the oxime. Moreover, the hydrogen atom was identified in circulation from the benzylic position of the substrates between AQN and 2-butanone to quench the carbon radical without requiring any additional reagents.
- Usami, Kaoru,Yamaguchi, Eiji,Tada, Norihiro,Itoh, Akichika
-
supporting information
p. 5714 - 5717
(2018/09/21)
-
- Synthesis and biological evaluation of 5-fatty-acylamido-1, 3, 4-thiadiazole-2-thioglycosides
-
In the present study, the synthesis of 1, 3, 4-thiadiazole-based thioglycosides were accomplished in good yields with employing a convergent synthetic route. The starting material 5-amino-1, 3, 4-thiadiazole-2-thiol and followed by a series of 5-fatty-acylamido-1, 3, 4-thiadiazole-2-thiols (4a–4j) were synthesized with different fatty acid chlorides. The glycosylation of compounds 4a–4j were achieved with trichloroacetimidate methodology. Antimicrobial and cytotoxicity activities of title compounds were evaluated. Among the entire compounds lauric acid and myristic acid derivatives showed good and moderate antimicrobial activity. In case of cytotoxicity results of compounds 8a–8j and 9a–9j, the acetate protected short chain (C6:0, C8:0, C10:0) compounds and the free hydroxyl long chain saturated (C16:0, C18:0) and unsaturated (C18:1, C22:1) compounds exhibited good activity against different cancer cell lines. Further, the free hydroxyl compounds 9a, 9c–9j did not show any toxicity towards normal CHO-K1 cell line whereas acylated compounds 8a–8j exhibited toxicity.
- Vudhgiri, Srikanth,Koude, Dhevendar,Veeragoni, Dileep Kumar,Misra, Sunil,Prasad,Jala, Ram Chandra Reddy
-
supporting information
p. 3370 - 3373
(2017/07/07)
-
- Photoinduced, Copper-Catalyzed Decarboxylative C-N Coupling to Generate Protected Amines: An Alternative to the Curtius Rearrangement
-
The Curtius rearrangement is a classic, powerful method for converting carboxylic acids into protected amines, but its widespread use is impeded by safety issues (the need to handle azides). We have developed an alternative to the Curtius rearrangement that employs a copper catalyst in combination with blue-LED irradiation to achieve the decarboxylative coupling of aliphatic carboxylic acid derivatives (specifically, readily available N-hydroxyphthalimide esters) to afford protected amines under mild conditions. This C-N bond-forming process is compatible with a wide array of functional groups, including an alcohol, aldehyde, epoxide, indole, nitroalkane, and sulfide. Control reactions and mechanistic studies are consistent with the hypothesis that copper species are engaged in both the photochemistry and the key bond-forming step, which occurs through out-of-cage coupling of an alkyl radical.
- Zhao, Wei,Wurz, Ryan P.,Peters, Jonas C.,Fu, Gregory C.
-
supporting information
p. 12153 - 12156
(2017/09/12)
-
- d-menthol fatty acid ester derivative, application thereof and preparation method for d-menthol fatty acid ester derivative
-
The invention belongs to the technical field of medicines and relates to a d-menthol fatty acid ester derivative, an application thereof and a preparation method for the d-menthol fatty acid ester derivative. The d-terpineol fatty acid ester is prepared through carrying out an esterification reaction on d-menthol and straight-chain fatty acid. The method comprises the steps of firstly, carrying out a reaction on fatty acid and thionyl chloride so as to prepare acyl chloride, and then, subjecting acyl chloride to a reaction with d-menthol, there by preparing the ester. The d-menthol ester is applied to external preparations such as plasters, cataplasm, ointment, gels, sprays and liniment as a penetration enhancer, so that the percutaneous absorption capacity of drugs, particularly, chiral drug enantiomers is increased; and the d-menthol ester is a very good percutaneous absorption penetration enhancer and has a broad application prospect.
- -
-
Paragraph 0032
(2017/08/29)
-
- Citronellol fatty acid ester derivative and application and preparation method thereof
-
The invention relates to a citronellol fatty acid ester derivative and an application and preparation method thereof. The citronellol fatty acid ester derivative is used as a transdermal absorption penetration enhancer for application and used for preparing a transdermal drug delivery preparation so that transdermal absorption of drugs can be improved, and the accumulative penetration amount of the drugs is increased. According to the citronellol fatty acid ester derivative, after reaction with thionyl chloride, fatty acyl chloride is prepared, then the fatty acyl chloride reacts with citronellol, and the citronellol fatty acid ester derivative is obtained. The citronellol fatty acid ester derivative can be applied to the transdermal drug delivery preparation, improves the penetration ability of the drugs, and can also be used as spice to mask the objectionable odor of the preparation.
- -
-
Paragraph 0051; 0052
(2017/12/09)
-
- Nerol aliphatic ester derivative as well as application and preparation method thereof
-
The invention belongs to the technical field of medicine, and relates to a nerol aliphatic ester derivative as well as application and a preparation method thereof. The nerol aliphatic ester is obtained by a esterification reaction between nerol and straight-chain fatty acid and is prepared from the following steps: preparing acyl chloride by reaction between fatty acid and sulfoxide chloride; preparing nerol aliphatic ester. by reaction between acyl chloride and nerol. The nerol aliphatic ester can be used as a penetration enhancer to be applied to external preparation, such as a patch, a cataplasm, an ointment, a gelling agent and a spraying agent, so that the percutaneous absorption of medicine is improved. The nerol aliphatic ester is a good percutaneous absorption enhancer and has a wide application prospect.
- -
-
Paragraph 0049; 0050
(2017/11/04)
-
- Lavandulol fatty acid ester derivative, application and preparation method thereof
-
The invention relates to a derivative, application and a preparation method of the derivative, in particular to a lavandulol fatty acid ester derivative, application and a preparation method thereof. The lavandulol fatty acid ester derivative is prepared by preparing fatty acyl chloride and then carrying out reaction with lavandulol. The lavandulol fatty acid ester derivative can be applied as a transdermal absorption penetration enhancer to prepare transdermal drug delivery preparations, and can improve transdermal absorption of drugs and increase the cumulative penetration amount of drugs. The compound provided by the invention can be applied to transdermal drug delivery preparations to strengthen the penetration performance of drugs, and also can be used as lavender alcohol fatty acid ester derivative, and its application and preparation method. Lavender fatty acid ester derivatives are prepared by preparing fatty acyl chloride and then reacting with lavender. As a percutaneous absorption and penetration enhancer, the transdermal drug preparation is prepared to improve the absorption of the drug and increase the cumulative permeation of the drug. The compounds described in the present invention can be used in the percutaneous drug delivery, enhance the permeation ability of the drug, and can also be used as a spice to cover up the objectionable odor of preparations.
- -
-
Paragraph 0006; 0007; 0050; 0051
(2017/12/27)
-
- Eugenol fatty acid ester derivative as well as application and preparation method thereof
-
The invention discloses a eugenol fatty acid ester derivative as well as application and a preparation method thereof. Eugenol fatty acid ester is obtained by an esterification reaction of eugenol and straight-chain fatty acid. The method comprises the following steps: firstly, preparing acyl chlorine by reacting fatty acid with thionyl chloride; mixing eugenol with an equal mole amount of pyridine or triethylamine; then, dropwise adding the prepared acyl chloride under the cooling action of an ice bath to generate the eugenol fatty acid ester. Eugenol ester can be applied to external preparations such as patches, cataplasm, ointments, gels and spray agents as a penetration enhancer in order to increase the transdermal absorption amount of medicaments, is a very good percutaneous absorption penetration enhancer, and has a wide application prospect.
- -
-
Paragraph 0052-0053
(2017/11/18)
-
- Linalool fatty acid ester type derivative as well as application and preparation method thereof
-
The invention belongs to the technical field of medicines and relates to a linalool fatty acid ester type derivative as well as application and a preparation method thereof. A fatty acid ester is obtained by carrying out esterification reaction on linalool and straight-chain fatty acid; the method comprises the following steps: firstly, taking fatty acid and sulfoxide chloride to react to prepare acyl chloride; taking the acyl chloride and the linalool to react to prepare ester. The linalool is used as a penetration enhancer and is applied to external preparations including patches, cataplasm, ointment, gel, spray, liniments and the like, so that the transdermal absorption amount of drugs, especially chiral drug enantiomers, is improved; the linalool fatty acid ester type derivative is a very good transdermal absorption penetration enhancer and has a wide application prospect.
- -
-
Paragraph 0047; 0048
(2018/01/03)
-
- Synthesis and Surface-Active Properties of a Homologous Series of Star-Like Triple-Chain Anionic Surfactants Derived from 1,1,1-Tris(hydroxymethyl)ethane
-
A novel homologous series of trimeric anionic surfactants, 3C n TE3CNa (where n is a fatty acid chain length of 7, 10, or 12), with three hydrocarbon chains and three carboxylate heads connected via tri-etheric bonds were synthesized from long-chain α-bromo fatty acids and a triol, 1,1,1-tris(hydroxymethyl)ethane. The obtained trimeric carboxylic acids were esterified and purified by silica gel column chromatography, then hydrolyzed with dilute sodium hydroxide solution to form a series of trimeric carboxylate surfactant products. All prepared compounds were analyzed by IR, 1H NMR, and 13C NMR spectroscopy to confirm their chemical structures. Their surface-active properties were investigated. The critical micelle concentrations (cmc) of 3C n TE3CNa were in the range of 0.12-0.71 mmol/L, and the surface tensions at the cmc (γ cmc) were 29.3-34.8 mN/m.
- Li, Xu,Xing, Fenglan,Xu, Qun,Sun, Xiaolong,Wang, Yuping,Wang, Liyan,Wang, Pinglang
-
p. 129 - 135
(2016/01/09)
-
- Iodobenzene Dichloride in the Esterification and Amidation of Carboxylic Acids: In-Situ Synthesis of Ph3PCl2
-
A novel, in-situ synthesis of dichlorotriphenylphosphorane (Ph3PCl2) is accomplished upon combining PPh3and the easily prepared hypervalent iodine reagent iodobenzene dichloride (PhICl2). The phosphorane is selectively generated in the presence of carboxylic acid or alcohol residues to rapidly produce acyl chlorides and alkyl chlorides in high yields. Addition of EtOH, PhOH, BnOH, Et2NH or CH2N2results in the direct synthesis of esters, amides and diazo ketones from carboxylic acids.
- Carle, Myriam S.,Shimokura, Grace K.,Murphy, Graham K.
-
supporting information
p. 3930 - 3933
(2016/08/24)
-
- Substituted pyrido[3′,4′:4,5]pyrrolo[1,2,3-de]quinoxalines for the treatment of nervous system disorders
-
The invention relates to particular substituted heterocycle fused gamma-carbolines, of Formula I as described herein, their prodrugs, in free, solid, pharmaceutically acceptable salt and/or substantially pure form as described herein, pharmaceutical compositions thereof, and methods of use in the treatment of diseases involving 5-HT2A receptor, serotonin transporter (SERT) and/or pathways involving dopamine D2 receptor signaling systems, such as diseases of the central nervous system.
- -
-
Page/Page column 33
(2016/07/27)
-
- Structure, supramolecular organization and phase behavior of N-acyl-β-alanines: Structural homologues of mammalian brain constituents N-acylglycine and N-acyl-GABA
-
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.
-
-
- 1, 1, 1-tri (hydroxymethyl) ethane as coupling includes sub-surfactant and method of preparing the same
-
The invenetion relates to a preparation method of a ternary surface active agent adopting 1,1,1-tri(hydroxymethyl) ethane as a link group. A structural formula of the ternary surface active agent is as follows (described in specifications). The synthesis method includes a synthesis step of alpha-bromo-carboxylic acid, an esterification reaction step of the link group 1,1,1-tri(hydroxymethyl) ethane and an esterolysis reaction step. The synthesis process condition of the ternary surface active agent is as follows: 30% NaOH and tetrahydrofuran are used as a solvent to be subjected to reflux reaction for 5 to 7 hours.
- -
-
Paragraph 0014; 0015; 0026; 0027
(2017/03/08)
-
- Α-terpineol fatty acid ester derivatives and use
-
The invention belongs to the technical field of medicine and discloses alpha-terpineol aliphatic ester and a preparation with the compound. The alpha-terpineol aliphatic ester is formed by alpha-terpineol and fatty acid after esterification reaction. According to a method, first, fatty acid and thionyl chloride react to prepare acyl chloride, and then acyl chloride and alpha-terpineol react to prepare the alpha-terpineol aliphatic ester. The alpha-terpineol ester can be used as penetration enhancers to be used for external preparations of patching agents, Cataplasm, ointment agents, gel agents and the like, accordingly, the percutaneous absorptive amount of medicine is improved, and the alpha-terpineol aliphatic ester is good percutaneous absorptive penetration enhancers and has wide application prospect.
- -
-
Paragraph 0051; 0052
(2017/03/18)
-
- Preparation and properties of a novel form-stable phase change material based on a gelator
-
A series of gelators (Gm, m is the length of the alkyl tails, m = 2, 4, 6, 8, 10, 12, 14, 16 and 18) containing 4,4′-diaminodiphenylmethane moieties were synthesized. The chemical structures of Gm were confirmed by 1H NMR and MS. The form-stable phase change materials (FSPCMs) were prepared by introducing Gm into paraffin. The minimum gelation concentration (MGC) and gel-to-sol transition temperature (TGS) properties were tested by the "tube-testing method". It found that Gm (m = 2, 4, 6) was insoluble in paraffin, while the MGC and TGS of Gm (m = 8, 10, 12, 14, 16, 18) increased with the increase of alkyl chain. The structure and morphology of the PCMs were systematically investigated by FT-IR, POM, 1D WXAD and SEM. Experimental results revealed that paraffin was restricted because the gelators could self-assemble into three-dimensional netted structures, leading to form the shape-stable PCMs without leakage even above their melting point. The thermal properties were studied by DSC. The research showed that the G18/paraffin FSPCMs exhibited excellent thermal stability and high heat storage density. The shape stability of G18/paraffin was investigated by rheological measurements, indicating that solid hard gel soft gel liquid was observed with the increase of temperature. This work is useful in the comprehensive academic research and industrial application of PCMs.
- Wu, Dang,Wen, Wen,Chen, Sheng,Zhang, Hailiang
-
supporting information
p. 2589 - 2600
(2015/02/19)
-
- Agent having neurotrophic factor-like activity
-
The present invention provides a pharmaceutical agent having high safety and a neurotrophic factor-like activity, which contains, as an active ingredient, any one compound included in fatty acids each having 8 carbon atoms (C8) or having 10 carbon atoms (C10) to 12 carbon atoms (C12) or fatty acid esters thereof, such as 3,7-dimethyloctanoic acid ethyl ester, geranicacidethyl ester, and the like, eachof whichhas 8 carbonatoms (C8), decanoic acid methyl ester, trans-2-decenoic acid, trans-2-decenoic acid methyl ester, trans-2-decenoic acid ethyl ester, trans-2-decenoic acid-2-decenyl ester, trans-2-decenoic acid cyclohexyl ester, trans-2-decenoic acid isopropyl ester, trans-3-decenoic acid methyl ester, trans-9-decenoic acid methyl ester, and the like, each of which has 10 carbon atoms (C10), trans-10-undecenoic acid methyl ester, trans-10-undecenoic acid ethyl ester, and the like, each of which has 11 carbon atoms (C11), and dodecanoic acid, and the like, each of which has 12 carbon atoms (C12), or salts thereof or prodrugs thereof.
- -
-
Paragraph 0025-0026
(2016/01/25)
-
- Using the same method and termiteproof termiteproof agent
-
PROBLEM TO BE SOLVED: To provide a termite-proofing agent exhibiting high termite-proofing effect and enabling its own production cost to be reduced, and to provide a termite-proofing method using the same. SOLUTION: The termite-proofing agent is provided, which includes an amide compound represented by general formula (1). In general formula (1), either one of X1and X2is a halogen atom, alkyl or (substituted) phenyl, the other being H; alternatively, the X1and X2are optionally bound to each other to form a (substituted) saturated or unsaturated 5- or 6-membered ring; Y is a 6-14C alkylene group; and Z is amido group including methyl, vinyl or two disubstituted groups. COPYRIGHT: (C)2012,JPOandINPIT
- -
-
Paragraph 0146
(2016/12/16)
-
- A practical in situ generation of the schwartz reagent. reduction of tertiary amides to aldehydes and hydrozirconation
-
A new, highly efficient in situ protocol (Cp2ZrCl2/LiAlH(OBu-t)3) is described for the generation of the Schwartz reagent which provides a convenient method for the amide to aldehyde reduction and the regioselective hydrozirconation-iodination of alkynes and alkenes. Highlighted are chemoselective reductions of benzamides derived by directed ortho metalation (DoM) chemistry, allowing the synthesis of valuable 1,2,3-substituted benzaldehydes. The single-step, three-component process proceeds in a very short reaction time, shows excellent functional group compatibility, and uses inexpensive and long-storage stable reducing reagents.
- Zhao, Yigang,Snieckus, Victor
-
supporting information
p. 390 - 393
(2014/04/03)
-
- Synthesis, characterization and biological evaluation of novel diesters of 4,4'-dihydroxy azoxy benzene with long chain carboxylic acids
-
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
-
p. 462 - 472
(2014/08/05)
-
- Synthesis and binding profile of haloperidol-based bivalent ligands targeting dopamine D2-like receptors
-
Homodimers of dopamine D2-like receptors are suggested to be of particular importance in the pathophysiology of schizophrenia and, thus, serve as promising targets for the discovery of atypical antipsychotics. This study describes the development of a series of novel bivalent molecules with a pharmacophore derived from the dopamine receptor antagonist haloperidol. These dimers were investigated in comparison to their monomeric analogues for their D2long, D2short, D3, and D4 receptor binding and the ability to bridge two neighboring receptor protomers. Radioligand binding studies provided diagnostic insights when Hill slopes close to two for the bivalent ligand 13 incorporating 22 spacer atoms and a comparative analysis with monovalent control ligands indicated a bivalent binding mode with a simultaneous occupancy of two neighboring binding sites.
- Salama, Ismail,L?ber, Stefan,Hübner, Harald,Gmeiner, Peter
-
supporting information
p. 3753 - 3756
(2014/09/16)
-
- Structure and thermotropic phase behavior of a homologous series of n -Acylglycines: Neuroactive and antinociceptive constituents of biomembranes
-
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.
-
p. 4944 - 4954
(2014/12/10)
-
- Organocatalytic oxidation of aldehydes to mixed anhydrides
-
TEMPO catalyzes the direct oxidation of aldehydes to mixed anhydrides in the presence of a carboxylic acid. The anhydrides can be converted in situ to esters, secondary, tertiary or Weinreb amides in high yield. Oxidation of the aldehyde directly to 2-propyl esters is also possible using only catalytic amounts of acid. The oxidation reactions are rapid and take place under mild conditions.
- Toledo, Hila,Pisarevsky, Evgeni,Abramovich, Adi,Szpilman, Alex M.
-
supporting information
p. 4367 - 4369
(2013/06/05)
-
- The relationship between the structure and properties of amino acid surfactants based on glycine and serine
-
Two series of surfactants based on glycine and serine were synthesized with aproic acid, octanoic acid, decanoic acid, dodecanoic acid, tetradecanoic acid and hexadecanoic acid. All the surfactants were characterized by MS and 1H NMR, the structures of the synthesized surfactants are correct and the signals in MS and 1H NMR can be explained. The reaction conditions, surface properties and foam properties were studied. For the two series of surfactants, critical micelle concentration (CMC) and γ CMC (surface tension at CMC) decrease and surface activity is enhanced as the length of carbon chain increases. The surfactants with tetradecanoyl and hexadecanoyl groups show a good foaming property and especially, the long-chain acyl-serine performs better. These are all related to the hydromethyl group in the serine.
- Qiao, Weihong,Qiao, Yangyang
-
p. 821 - 828
(2013/11/06)
-
- Inhibition of PCAF histone acetyltransferase and cytotoxic effect of N-acylanthranilic acids
-
Small molecule HAT inhibitors are useful tools to unravel the role of histone acetyltransferases (HATs) in the cell and have relevance for oncology. We synthesized a series of N-acylanthranilic acids (11-16) and of N-acyl-5-hydroxyanthranilic acids (17-22) bearing C6, C8, C10, C12, C14, along with C16 acyl chain at the 2-amino position of anthranilic acid or 5-hydroxyanthranilic acid. Enzyme inhibition of these compounds was investigated, using in vitro PCAF HAT assays. All synthesized compounds (65-76%) showed similar inhibitory activity to anacardic acid (68%) at 100 μM. The cytotoxicity, against one normal cell line (HSF) and eight cancer cell lines (HT-29, HCT-116, MDA-231, A-549, Hep3B, Caski, HeLa and Caki), were evaluated by the SRB method.
- Park, Woong Jae,Ma, Eunsook
-
p. 1379 - 1386
(2013/01/15)
-
- Inhibition of PCAF histone acetyltransferase, cytotoxicity and cell permeability of 2-acylamino-1-(3-or 4-carboxy-phenyl)benzamides
-
Small molecule HAT inhibitors are useful tools to unravel the role of histone acetyltransferases (HATs) in the cell and they also have relevance in oncology. We synthesized a series of 2-acylamino-1-(3- or 4-carboxyphenyl) benzamides 8-19 bearing C6, C8, C10, C12, C14, and C16 acyl chains at the 2-amino position of 2-aminobenzoic acid. Enzyme inhibition of these compounds was investigated using in vitro PCAF HAT assays. The inhibitory activities of compounds 8-10, 16, and 19 were similar to that of anacardic acid, and 17 was found to be more active than anacardic acid at 100 μM. Compounds 11-15 showed the low inhibitory activity on PCAF HAT. The cytotoxicity of the synthesized compounds was evaluated by SRB (sulforhodamine B) assay against seven human cancer cell lines: HT-29 (colon), HCT-116 (colon), MDA-231 (breast), A549 (lung), Hep3B (hepatoma), HeLa (cervical) and Caki (kidney) and one normal cell line (HSF). Compound 17 was more active than anacardic acid against human colon cancer (HCT 116, IC50: 29.17 μM), human lung cancer (A549, IC 50: 32.09 μM) cell lines. 18 was more active than anacardic acid against human colon cancer (HT-29, IC50: 35.49 μM and HCT 116, IC50: 27.56 μM), human lung cancer (A549, IC50: 30.69 μM), and human cervical cancer (HeLa, IC50: 34.41 μM) cell lines. The apparent permeability coefficient (Papp, cm/s) values of two compounds (16 and 17) were evaluated as 68.21 and 71.48 × 10 -6 cm/s by Caco-2 cell permeability assay.
- Park, Woong Jae,Ma, Eunsook
-
p. 13116 - 13131
(2013/02/22)
-
- Synthesis, modelling and kinetic assays of potent inhibitors of purple acid phosphatase
-
Purple acid phosphatases (PAPs) are binuclear metallohydrolases that have been isolated from various mammals, plants, fungi and bacteria. In mammals PAP activity is associated with bone resorption and can lead to bone metabolic disorders such as osteoporosis; thus human PAP is an attractive target to develop anti-osteoporotic drugs. Based on a previous lead compound and rational drug design, acyl derivatives of α-aminonaphthylmethylphosphonic acid were synthesised and tested as PAP inhibitors. Kinetic analysis showed that they are good PAP inhibitors whose potencies improve with increasing acyl chain length. Maximum potency is reached when the number of carbons in the acyl chain is between 12 and 14. The most potent inhibitor of red kidney bean PAP is the dodecyl-derivative with Kic = 5 μM, while the most potent pig PAP inhibitor is the tetradecyl-derivative with Kic = 8 μM, the most potent inhibitor of a mammalian PAP yet reported.
- Mohd-Pahmi, Siti Hajar,Hussein, Waleed M.,Schenk, Gerhard,McGeary, Ross P.
-
supporting information; experimental part
p. 3092 - 3094
(2011/06/24)
-
- Synthesis and biological evaluation of novel aliphatic amido-quaternary ammonium salts for anticancer chemotherapy: Part i
-
We synthesized novel aliphatic amido-quaternary ammonium salts in an effort to discover anticancer agents that increase Ras homolog gene family, member B, (RhoB) levels. These compounds exert anti-proliferative activities against several human cancer cell types. Seventeen compounds, varying in aliphatic carbon chain length and N-substituents, were synthesized and their biological activities were evaluated. Of these 17 compounds, compound 3i emerged as the most promising anticancer compound by promoting apoptosis through the RhoB mediated pathway. Potent biological activities observed for these novel aliphatic amido-quaternary ammonium salt analogues support their potential as anticancer, chemotherapeutic agents.
- Yang, Jee Sun,Song, Doona,Lee, Boah,Ko, Won Jin,Park, Song-Kyu,Won, Misun,Lee, Kiho,Kim, Hwan Mook,Han, Gyoonhee
-
experimental part
p. 2861 - 2866
(2011/06/27)
-
- Synthesis, antimicrobial evaluation, QSAR and in silico ADMET studies of decanoic acid derivatives
-
Various derivatives of decanoic acid (CD) have been synthesized and evaluated against Gram positive B. subtilis, S. aureus and Gram negative E. coli bacteria as well as against fungi C. albicans and A. niger. Quantitative structure activity relationship (QSAR) models for antimicrobial activities were developed using multiple linear regression and cross validated by leave one out (LOO) approach. QSAR studies indicated that activity against Gram positive bacteria was governed by lipophilicity of the compounds while topological steric nature of the molecule was deciding factor for antifungal activity. Further, in silico ADMET studies showed that compounds CD12, 19, 20 and 23 could be explored further for other activities.
- Kumar, Ashwani,Singh, Surender,Jain, Sandeep,Kumar, Parvin
-
scheme or table
p. 191 - 204
(2011/10/09)
-
- Hydrophobic modification of chitosan and its physicochemical evaluation as sustained release tablet formulation
-
Chitosan is being investigated widely for use as an excipient in oral and other pharmaceutical formulations. Chitosan is generally regarded as a nontoxic and non-irritant material. It is biocompatible with both healthy and infected skin. Chitosan has been shown to be biodegradable (LD50 (mouse, oral): > 16 g/kg). Unmodified chitosan exhibited a low degree of disorder and a weak tablet crushing strength. In the present work, the hydrophobically modified chitosan were synthesized in order to formulate a system for sustain release of hydrophilic drug (indomethacine prototype drug in present case). The caproyl (C-8), decanoyl (C-10), lauryl (C-12), myristyl (C-14), palmitoyl (C-16) and stearoyl (C-18), fatty acyl derivatives of chitosan were prepared and physicochemically evaluated as excipient in matrix tablet dosage. The best sustained release studies was defined by palmitoyl chitosan and it can able sustain 50-60 % release upto 12 h and in concentration range 10-30 % much less as compared to chitosan ( > 50 %).
- Singh,Tiwari
-
experimental part
p. 2141 - 2150
(2012/02/14)
-
- Synthesis and critical micelle concentration of a series of gemini alkylphenol polyoxyethylene nonionic surfactants
-
A series of gemini n-alkylphenol polyoxyethylene surfactants (GAP) were successfully synthesized and their molecular structure were confirmed by NMR and FTIR spectrum. Using the same synthesis route, a Gemini nonylphenol polyoxyethylene surfactant (GNP) was synthesized using an industrial nonylphenol product and paraformaldehyde, and its molecular structure was also characterized by 1H-NMR and FTIR spectra. The optimal reaction conditions were established. The critical micelle concentration (CMC) values of GAP were determined by means of Wilhelmy plate method and steady-state fluorescence probe method. The experimental results show how the lengths of the hydrophilic polyoxyethylene chain and the hydrophobic tail alter the CMC values. The CMC values of the GAP are found to be much lower than those of corresponding conventional single tail nonionic surfactants of the polyethoxylated alkylphenol type, which indicates that the gemini species exhibit a better surface activity. AOCS 2011.
- Yang, Fang,Li, Gang,Xu, Nian,Liu, Rong,Zhang, Song-Mei,Wu, Zeng-Jiang
-
experimental part
p. 339 - 345
(2012/06/30)
-
