- N-Amino-1,8-Naphthalimide is a Regenerated Protecting Group for Selective Synthesis of Mono-N-Substituted Hydrazines and Hydrazides
-
A new route to synthesis of various mono-N-substituted hydrazines and hydrazides by involving in a new C?N bond formation by using N-amino-1,8-naphthalimide as a regenerated precursor was invented. Aniline and phenylhydrazines are reproduced upon reacting these individually with 1,8-naphthalic anhydride followed by hydrazinolysis. The practicality and simplicity of this C?N dihalo alkanes; developed a synthon for bond formation protocol was exemplified to various hydrazines and hydrazides. N-amino-1,8-naphthalimide is suitable synthon for transformation for selective formation of mono-substituted hydrazine and hydrazide derivatives. Those are selective mono-amidation of hydrazine with acid halides; mono-N-substituted hydrazones from aldehydes; synthesis of N-aminoazacycloalkanes from acetohydrazide scaffold and inserted to hydroxy derivatives; distinct synthesis of N,N-dibenzylhydrazines and N-benzylhydrazines from benzyl halides; synthesis of N-amino-amino acids from α-halo esters. Ecofriendly reagent N-amino-1,8-naphthalimide was regenerated with good yields by the hydrazinolysis in all procedures.
- Manoj Kumar, Mesram,Venkataramana, Parikibanda,Yadagiri Swamy, Parikibanda,Chityala, Yadaiah
-
supporting information
p. 17713 - 17721
(2021/11/10)
-
- Design, Synthesis, and Pharmacological Evaluation of First-in-Class Multitarget N-Acylhydrazone Derivatives as Selective HDAC6/8 and PI3Kα Inhibitors
-
Targeting histone deacetylases (HDACs) and phosphatidylinositol 3-kinases (PI3Ks) is a very promising approach for cancer treatment. This manuscript describes the design, synthesis, in vitro pharmacological profile, and molecular modeling of a novel class of N-acylhydrazone (NAH) derivatives that act as HDAC6/8 and PI3Kα dual inhibitors. The surprising selectivity for PI3Kα may be related to differences in the conformation in the active site. Cellular studies showed that these compounds act in HDAC6 inhibition and the PI3/K/AKT/mTOR pathway. The compounds that are selective for inhibition of HDAC6/8 and inhibit PI3Kα show potential for the treatment of cancer.
- Alves, Marina A.,Chaves, Lorrane S.,Fernandes, Patrícia D.,Fraga, Carlos A. M.,Guerra, Fabiana S.,Rodrigues, Daniel A.,Sagrillo, Fernanda S.,Sant'Anna, Carlos M. R.,Thota, Sreekanth,de Sena M. Pinheiro, Pedro
-
supporting information
(2020/02/25)
-
- 4-Amino-1,2,4-triazole-3-thione-derived Schiff bases as metallo-β-lactamase inhibitors
-
Resistance to β-lactam antibiotics in Gram-negatives producing metallo-β-lactamases (MBLs) represents a major medical threat and there is an extremely urgent need to develop clinically useful inhibitors. We previously reported the original binding mode of 5-substituted-4-amino/H-1,2,4-triazole-3-thione compounds in the catalytic site of an MBL. Moreover, we showed that, although moderately potent, they represented a promising basis for the development of broad-spectrum MBL inhibitors. Here, we synthesized and characterized a large number of 4-amino-1,2,4-triazole-3-thione-derived Schiff bases. Compared to the previous series, the presence of an aryl moiety at position 4 afforded an average 10-fold increase in potency. Among 90 synthetic compounds, more than half inhibited at least one of the six tested MBLs (L1, VIM-4, VIM-2, NDM-1, IMP-1, CphA) with Ki values in the μM to sub-μM range. Several were broad-spectrum inhibitors, also inhibiting the most clinically relevant VIM-2 and NDM-1. Active compounds generally contained halogenated, bicyclic aryl or phenolic moieties at position 5, and one substituent among o-benzoic, 2,4-dihydroxyphenyl, p-benzyloxyphenyl or 3-(m-benzoyl)-phenyl at position 4. The crystallographic structure of VIM-2 in complex with an inhibitor showed the expected binding between the triazole-thione moiety and the dinuclear centre and also revealed a network of interactions involving Phe61, Tyr67, Trp87 and the conserved Asn233. Microbiological analysis suggested that the potentiation activity of the compounds was limited by poor outer membrane penetration or efflux. This was supported by the ability of one compound to restore the susceptibility of an NDM-1-producing E. coli clinical strain toward several β-lactams in the presence only of a sub-inhibitory concentration of colistin, a permeabilizing agent. Finally, some compounds were tested against the structurally similar di-zinc human glyoxalase II and found weaker inhibitors of the latter enzyme, thus showing a promising selectivity towards MBLs.
- Baud, Damien,Bebrone, Carine,Becker, Katja,Benvenuti, Manuela,Cerboni, Giulia,Chelini, Giulia,Cutolo, Giuliano,De Luca, Filomena,Docquier, Jean-Denis,Feller, Georges,Fischer, Marina,Galleni, Moreno,Gavara, Laurent,Gresh, Nohad,Kwapien, Karolina,Legru, Alice,Mangani, Stefano,Mercuri, Paola,Pozzi, Cecilia,Sannio, Filomena,Sevaille, Laurent,Tanfoni, Silvia,Verdirosa, Federica,Berthomieu, Dorothée,Bestgen, Beno?t,Frère, Jean-Marie,Hernandez, Jean-Fran?ois
-
-
- New gold (I) complexes with 5-aromatic ring-1, 3, 4-oxadiazole-2-thione and triphenylphosphine as potential multifunctional materials
-
Three new gold (I) complexes (4a, 4b, 4c) with 5-aromatic ring-1, 3, 4-oxadiazole-2-thione and triphenylphosphine as ligands were synthesized. Structures of 4a and 4b were determined through X-ray single-crystal diffraction, and it displayed that 4a and 4b had the same metal coordination pattern, wherein the ligand was coordinated by the sulfur atom to the central metal ion of gold (I). The optical properties of these gold (I) complexes were studied both in solution and in solid-state. In DMSO, 4a and 4b peaked at 415 nm and 443 nm, respectively, and the CIE coordinates of 4a and 4b in the solid-state were in the green area namely, (0.26, 0.46) and (0.24, 0.41). HOMO/LUMO levels and bandgaps of 4a, 4b and 4c were assessed by UV spectrum estimation, electrochemical method, and theoretical calculations. The observation hinted that the photophysical properties and energy levels of these gold (I) complexes can be adjusted by the introduction of different substituent aromatic rings at the 5-position of the 1, 3, 4-oxadiazole-2-thiol moiety. The findings of good optical, electrochemical and thermal properties of these new gold (I) complexes demonstrated their potential in the future studies as multifunctional materials.
- Zhao, Yu Qiang,Zhou, Jie,He, Renze,Wang, Guang Ke,Miao, Lan Xi,Xie, Xiao Guang,Zhou, Ying
-
-
- Synthesis and structural study of some N-acyl-4-allylsemicarbazides and the product of their cyclization with a potential antimicrobial activity
-
In this paper semicarbazide (2a-2h) and 1,2,4-trazole (3a-3h) derivatives with allyl group were synthesized. All compounds were tested in vitro for their antimicrobial activity showing different activity to E. coli, S. aureus, S. epidermidis, M. smegmatis, M. phlei and M. tuberculosis H37Ra. The antimicrobial activity is showed 2g against S. epidermidis, 3g against E. coli and S. epidermidis and 3h against E. coli. The crystal structure of determinations of 2b, 2d, 3b, 3c and 3e were undertaken in order to confirm the synthesis pathway and identification of their tautomeric forms in the crystalline state. Theoretical calculations showed that the physico-chemicals (logP) and electronic properties (MEP distribution, energy localization of HOMO and LUMO orbitals) are related to observed antimicrobial activity of investigated compounds. The molecular docking study carried out for the most active against M. tuberculosis compound 3b using the M. tuberculosis cytochrome P450 CYP121 showed that this compound binds to the active site of P450 by hydrogen bonds via water molecule with the amino acid residue of Met86A and molecule of hem.
- Drozd, Monika,Ginalska, Grazyna,Karczmarzyk, Zbigniew,Kowalczuk, Dorota,Morawiak, Maja,Pitucha, Monika,Swatko-Ossor, Marta,Urbanczyk-Lipkowska, Zofia,Wysocki, Waldemar
-
-
- Structure-Activity Relationships of Nitro-Substituted Aroylhydrazone Iron Chelators with Antioxidant and Antiproliferative Activities
-
Aroylhydrazone iron chelators such as salicylaldehyde isonicotinoyl hydrazone (SIH) protect various cells against oxidative injury and display antineoplastic activities. Previous studies have shown that a nitro-substituted hydrazone, namely, NHAPI, displayed markedly improved plasma stability, selective antitumor activity, and moderate antioxidant properties. In this study, we prepared four series of novel NHAPI derivatives and explored their iron chelation activities, anti- or pro-oxidant effects, protection against model oxidative injury in the H9c2 cell line derived from rat embryonic cardiac myoblasts, cytotoxicities to the corresponding noncancerous H9c2 cells, and antiproliferative activities against the MCF-7 human breast adenocarcinoma and HL-60 human promyelocytic leukemia cell lines. Nitro substitution had both negative and positive effects on the examined properties, and we identified new structure-activity relationships. Naphthyl and biphenyl derivatives showed selective antiproliferative action, particularly in the breast adenocarcinoma MCF-7 cell line, where they exceeded the selectivity of the parent compound NHAPI. Of particular interest is a compound prepared from 2-hydroxy-5-methyl-3-nitroacetophenone and biphenyl-4-carbohydrazide, which protected cardiomyoblasts against oxidative injury at 1.8 ± 1.2 μM with 24-fold higher selectivity than SIH. These compounds will serve as leads for further structural optimization and mechanistic studies.
- Hru?ková, Kate?ina,Pot??ková, Eli?ka,Opálka, Luká?,Hergeselová, Tereza,Ha?ková, Pavlína,Kova?íková, Petra,?im?nek, Tomá?,Vávrová, Kate?ina
-
p. 435 - 446
(2018/05/29)
-
- HISTONE DEACETYLASE INHIBITORS AND USES THEREOF
-
Provided herein are compounds of the formula (I) as well as pharmaceutically acceptable salts thereof, wherein the substituents are as those disclosed in the specification. These compounds, and the pharmaceutical compositions containing them, are useful for the treatment of cancer.
- -
-
Page/Page column 22; 26
(2018/04/27)
-
- 1,2,4-Triazole-3-thione Compounds as Inhibitors of Dizinc Metallo-β-lactamases
-
Metallo-β-lactamases (MBLs) cause resistance of Gram-negative bacteria to β-lactam antibiotics and are of serious concern, because they can inactivate the last-resort carbapenems and because MBL inhibitors of clinical value are still lacking. We previously identified the original binding mode of 4-amino-2,4-dihydro-5-(2-methylphenyl)-3H-1,2,4-triazole-3-thione (compound IIIA) within the dizinc active site of the L1 MBL. Herein we present the crystallographic structure of a complex of L1 with the corresponding non-amino compound IIIB (1,2-dihydro-5-(2-methylphenyl)-3H-1,2,4-triazole-3-thione). Unexpectedly, the binding mode of IIIB was similar but reverse to that of IIIA. The 3 D structures suggested that the triazole–thione scaffold was suitable to bind to the catalytic site of dizinc metalloenzymes. On the basis of these results, we synthesized 54 analogues of IIIA or IIIB. Nineteen showed IC50 values in the micromolar range toward at least one of five representative MBLs (i.e., L1, VIM-4, VIM-2, NDM-1, and IMP-1). Five of these exhibited a significant inhibition of at least four enzymes, including NDM-1, VIM-2, and IMP-1. Active compounds mainly featured either halogen or bulky bicyclic aryl substituents. Finally, some compounds were also tested on several microbial dinuclear zinc-dependent hydrolases belonging to the MBL-fold superfamily (i.e., endonucleases and glyoxalase II) to explore their activity toward structurally similar but functionally distinct enzymes. Whereas the bacterial tRNases were not inhibited, the best IC50 values toward plasmodial glyoxalase II were in the 10 μm range.
- Sevaille, Laurent,Gavara, Laurent,Bebrone, Carine,De Luca, Filomena,Nauton, Lionel,Achard, Maud,Mercuri, Paola,Tanfoni, Silvia,Borgianni, Luisa,Guyon, Carole,Lonjon, Pauline,Turan-Zitouni, Gülhan,Dzieciolowski, Julia,Becker, Katja,Bénard, Lionel,Condon, Ciaran,Maillard, Ludovic,Martinez, Jean,Frère, Jean-Marie,Dideberg, Otto,Galleni, Moreno,Docquier, Jean-Denis,Hernandez, Jean-Fran?ois
-
p. 972 - 985
(2017/06/27)
-
- Aroylhydrazone iron chelators: Tuning antioxidant and antiproliferative properties by hydrazide modifications
-
Aroylhydrazones such as salicylaldehyde isonicotinoyl hydrazone (SIH) are tridentate iron chelators that may possess antioxidant and/or antineoplastic activities. Their main drawback, their low stability in plasma, has recently been partially overcome by exchanging the aldimine hydrogen for an unbranched alkyl group. In this study, ten analogs of methyl- and ethyl-substituted SIH derivatives with modified hydrazide scaffolds were synthesized to further explore their structure-activity relationships. Their iron-chelation efficiencies, anti- or pro-oxidant potentials, abilities to induce protection against model oxidative injury on the H9c2 cell line derived from rat embryonic cardiac tissue, cytotoxicities on the same H9c2 cells and antiproliferative activities on MCF-7 human breast adenocarcinoma and HL-60 human promyelotic leukemia cell lines were evaluated. Compounds derived from lipophilic naphthyl and biphenyl hydrazides displayed highly selective antiproliferative activities against both MCF-7 and HL-60 cell lines, and they showed markedly improved stabilities in plasma compared to SIH. Of particular interest is a hydrazone prepared from 2-hydroxypropiophenone and pyridazin-4-carbohydrazide that showed a considerable antiproliferative effect and protected cardiomyoblasts against oxidative stress with a five-fold higher selectivity compared to the parent compound SIH. Thus, this work highlighted new structure-activity relationships among antiproliferative and antioxidant aroylhydrazones and identified new lead compounds for further development.
- Hru?ková, Kate?ina,Pot??ková, Eli?ka,Hergeselová, Tereza,Liptáková, Lucie,Ha?ková, Pavlína,Mingas, Panagiotis,Kova?íková, Petra,?im?nek, Tomá?,Vávrová, Kate?ina
-
-
- Development of Allosteric Hydrazide-Containing Class i Histone Deacetylase Inhibitors for Use in Acute Myeloid Leukemia
-
One of the biggest hurdles yet to be overcome for the continued improvement of histone deacetylase (HDAC) inhibitors is finding alternative motifs equipotent to the classic and ubiquitously used hydroxamic acid. The N-hydroxyl group of this motif is highly subject to sulfation/glucoronidation-based inactivation in humans; compounds containing this motif require much higher dosing in clinic to achieve therapeutic concentrations. With the goal of developing a second generation of HDAC inhibitors lacking this hydroxamate, we designed a series of potent and selective class I HDAC inhibitors using a hydrazide motif. These inhibitors are impervious to glucuronidation and demonstrate allosteric inhibition. In vitro and ex vivo characterization of our lead analogues' efficacy, selectivity, and toxicity profiles demonstrate that they possess low nanomolar activity against models of acute myeloid leukemia (AML) and are at least 100-fold more selective for AML than solid immortalized cells such as HEK293 or human peripheral blood mononuclear cells.
- McClure, Jesse J.,Zhang, Cheng,Inks, Elizabeth S.,Peterson, Yuri K.,Li, Jiaying,James Chou
-
p. 9942 - 9959
(2016/11/19)
-
- Fluorescent chemodosimeter based on spirobenzopyran for organophosphorus nerve agent mimics (DCP)
-
A new chromogenic as well as fluorogenic protocol based on the spirobenzopyran system for the selective detection of nerve agent mimics (diethyl chlorophosphate or DCP vapour) within a few seconds (～30 s) is designed, synthesized and characterized in this study. The nucleophilic attack from the oxygen atom of the spiro ring on the electrophilic phosphonyl group of DCP (diethyl chlorophosphate) causes the opening of the spiro (SP) framework and ultimately gives rise to the meta stable merocyanine (MC) form to give a fluorescent species, which gives a signal in the red region (～675 nm). The 'turn-on' red fluorescence and a colorimetric change from colourless to yellow was observed upon the addition of DCP, which evokes almost 124 and 84 fold enhancement in the absorbance and emission intensity, respectively, compare to the probe itself. To the best of our knowledge, such a DCP sensor based on the spirobenzopyran network has not been reported to date. Moreover, the detection limit of this probe was found to be in 10-8 M level in the solution phase. We also developed it as a portable chemosensor kit for DCP and demonstrated its practical application in real-time monitoring. This journal is
- Goswami, Shyamaprosad,Das, Sangita,Aich, Krishnendu
-
p. 28996 - 29001
(2015/04/14)
-
- Ultrasound-assisted, one-pot, three-component synthesis and antibacterial activities of novel indole derivatives containing 1,3,4-oxadiazole and 1,2,4-triazole moieties
-
Thirteen novel indole derivatives were efficiently synthesized through ultrasound irradiation by using 4-amino-5-(1H-indol-3-yl)-4H-[1,2,4]triazole-3-thiol (8) and 2-mercapto-5-substituted-1,3,4-oxadiazoles (5a-m). Compared with conventional and microwave methods, yields increased to 82-93%, and reaction times decreased to 15-35 min. The structures of these novel compounds were characterized by spectral data and elemental analysis. Two out of the synthesized compounds (10f and 10l) exhibited excellent activity against Staphylococcus aureus and Escherichia coli, and thus warrant further research.
- Shi, Zhichuan,Zhao, Zhigang,Huang, Meiwei,Fu, Xiaolin
-
p. 1320 - 1327
(2015/12/11)
-
- Acid Chloride Synthesis by the Palladium-Catalyzed Chlorocarbonylation of Aryl Bromides
-
We report a palladium-catalyzed method to synthesize acid chlorides by the chlorocarbonylation of aryl bromides. Mechanistic studies suggest the combination of sterically encumbered PtBu3 and CO coordination to palladium can rapidly equilibrate the oxidative addition/reductive elimination of carbon-halogen bonds. This provides a useful method to assemble highly reactive acid chlorides from stable and available reagents, and can be coupled with subsequent nucleophilic reactions to generate new classes of carbonylated products. The Good, the Bad and the Bulky! By employing a sterically encumbered phosphine ligand, tri-tert-butyl phosphine, under palladium catalysis inert aryl bromides are chlorocarbonylated to create reactive acid chlorides by reversible carbon-halogen bond reductive elimination. This general platform allows for an expanded scope of the Heck carbonylation reaction to include previously incompatible nucleophiles.
- Quesnel, Jeffrey S.,Kayser, Laure V.,Fabrikant, Alexander,Arndtsen, Bruce A.
-
supporting information
p. 9550 - 9555
(2015/06/30)
-
- Novel arylhydrazone derivatives bearing a rhodanine moiety: Synthesis and evaluation of their antibacterial activities
-
A series of arylhydrazone derivatives bearing a rhodanine moiety have been synthesized, characterized, and evaluated as antibacterial agents. Some of these compounds showed potent antibacterial activities against several different strains of Gram-positive bacteria, including multidrug-resistant clinical isolates. Of the compounds tested, IIk and IIIk were identified as the most effective, with minimum inhibitory concentration values of 2-4 μg/mL against multidrug-resistant Gram-positive organisms, including methicillin-resistant and quinolone-resistant Staphylococcus aureus. None of the compounds exhibited any activity against the Gram-negative bacteria Escherichia coli 1356 at 64 μg/mL.
- Li, Wei,Zheng, Chang-Ji,Sun, Liang-Peng,Song, Ming-Xia,Wu, Yan,Li, Yin-Jing,Liu, Yi,Piao, Hu-Ri
-
p. 852 - 861
(2014/08/05)
-
- Novel 1,3,4-oxadiazole thioether derivatives targeting thymidylate synthase as dual anticancer/antimicrobial agents
-
A series of novel 1,3,4-oxadiazole thioether derivatives (compounds 9-44) were designed and synthesized as potential inhibitors of thymidylate synthase (TS) and as anticancer agents. The in vitro anticancer activities of these compounds were evaluated against three cancer cell lines by the MTT method. Among all the designed compounds, compound 18 bearing a nitro substituent exhibited more potent in vitro anticancer activities with IC50 values of 0.7 ± 0.2, 30.0 ± 1.2, 18.3 ± 1.4 μM, respectively, which was superior to the positive control. In the further study, it was identified as the most potent inhibitor against two kinds of TS protein (for human TS and Escherichia coli TS, IC50 values: 0.62 and 0.47 μM, respectively) in the TS inhibition assay in vitro and the most potent antibacterial agents with MIC (minimum inhibitory concentrations) of 1.56-3.13 μg/mL against the tested four bacterial strains. Molecular docking and 3D-QSAR study supported that compound 18 can be selected as dual antitumor/antibacterial candidate in the future study.
- Du, Qian-Ru,Li, Dong-Dong,Pi, Ya-Zhou,Li, Jing-Ran,Sun, Jian,Fang, Fei,Zhong, Wei-Qing,Gong, Hai-Bin,Zhu, Hai-Liang
-
p. 2286 - 2297
(2013/05/09)
-
- Microwave-assisted synthesis and antibacterial activity of methyl 1-{2-[4-amino-5-(naphthalen-1-yl)-4H-1,2,4-triazol-3-ylthio]ethyl} -1H-indole-3-carboxylate derivatives
-
Twelve new Schiff bases containing a disubstituted 1,2,4-triazole and a monosubstituted indole linked by a thioethyl group were efficiently synthesised via a method employing microwave irradiation. Compared with a conventional method of heating at 100 °C, yields were increased from 46-48 to 82-92% and the reaction times were reduced from 20-25 h to 4-7 min. The structures of these novel hexacyclic Schiff bases were characterised by their spectral data and elemental analysis. Evaluation of their antibacterial activity showed that many of them possess excellent activity against Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa and Bacillus subtilis.
- Peng, Yongle,Liu, Xingli,Gu, Jian,Zhao, Zhigang
-
p. 413 - 416
(2013/09/12)
-
- Synthesis, biological evaluation and molecular docking studies of novel 2-(1,3,4-oxadiazol-2-ylthio)-1-phenylethanone derivatives
-
In present study, a series of new 2-(1,3,4-oxadiazol-2-ylthio)-1- phenylethanone derivatives (6a-6x) as potential focal adhesion kinase (FAK) inhibitors were synthesized. The bioassay assays demonstrated that compound 6i showed the most potent activity, which inhibited the growth of MCF-7 and A431 cell lines with IC50 values of 140 ± 10 nM and 10 ± 1 nM, respectively. Compound 6i also exhibited significant FAK inhibitory activity (IC50 = 20 ± 1 nM). Docking simulation was performed to position compound 6i into the active site of FAK to determine the probable binding model.
- Zhang, Li-Rong,Liu, Zhi-Jun,Zhang, Hui,Sun, Jian,Luo, Yin,Zhao, Ting-Ting,Gong, Hai-Bin,Zhu, Hai-Liang
-
scheme or table
p. 3615 - 3621
(2012/07/27)
-
- Synthesis using microwave irradiation, characterisation and antibacterial activity of Novel deoxycholic acid-triazole conjugates
-
Novel deoxycholic acid 3α-triazole conjugates based on methyl 3α-chloroacetoxy-12α-hydroxy-cholanate have been synthesised. The synthesis is accelerated by microwave irradiation under solvent free conditions in the presence of K2CO3. Some of these compounds were tested for antibacterial activity against B.subtilis, P.aeruginosa and S.aureus. The preliminary results indicated that these deoxycholic acid-triazole conjugates have good inhibitory effect against B.subtilis. All of the compounds were characterised by 1H NMR, IR, ESI-MS spectra and elemental analyses.
- Yang, Jie,Zhao, Zhigang,Li, Hui
-
p. 383 - 386
(2012/10/08)
-
- Synthesis of 1,6-hexanediyl-bis(semicarbazides) and 1,6-hexanediyl-bis(1,2, 4-triazol-5-ones) and their antiproliferative and antimicrobial activity
-
A series of 1,6-bis(3-substituted 1,5-dihydro-5-oxo-4H-1,2,4-triazol- -4-yl)hexanes 3a-g were synthesized by the cyclization reaction of 1,6-bis{[(2- -substituted hydrazinyl)carbonyl]amino}hexanes 2a-g in alkaline medium. The new derivatives 3a-c were screened in vitro for their antiproliferative and anticancer activity in human tumor cell lines derived from breast and lung carcinoma cells. Compounds 3a (at a concentration of 0.18 mM), 3b (at concentrations of 0.12 and 0.02 mM) and 3c (at concentrations of 0.23 and 0.11 mM) were found to be the most effective against the lung cell line. Compound 3a had the greatest antiproliferative effect on the breast carcinoma cell line. Representative compounds were established and evaluated as antimicrobial agents. All the tested derivatives showed minimum inhibitory concentrations (MIC) in the range 1.87-7.5 μg mL-1. Compound 3b was the most effective against Candida albicans (MIC 1.87 μg mL-1). Copyright 2012 (CC) SCS.
- Pitucha, Monika,Rzymowska, Jolanta,Olender, Alina,Grzybowska-Szatkowska, Ludmia
-
scheme or table
p. 1 - 8
(2012/05/05)
-
- A metal-free route to 2-aminooxazoles by taking advantage of the unique ring opening of benzoxazoles and oxadiazoles with secondary amines
-
Toss an amine into the ring: A new metal-free protocol for the amination of oxazoles has been developed by using iodobenzene diacetate to couple various oxazoles with amines (see scheme). The reaction proceeds through a ring-opening and subsequent ring-closing pathway. The optimal conditions are very mild and the substrate scope is broad, producing a range of 2-aminooxazoles, an important pharmacophore with high bioactivity. Copyright
- Joseph, Jomy,Kim, Ji Young,Chang, Sukbok
-
supporting information; experimental part
p. 8294 - 8298
(2011/08/21)
-
- Synthesis of new Schiff bases derived from dimers of 4-amino-3-(1-naphthyl) -5-thiomethyl-1, 2, 4-triazole using microwave irradiation
-
An efficient method for the synthesis of novel Schiff bases derived from dimers of 4-amino-3-(1-naphthyl)-5-thiomethyl-1, 2, 4-triazole using microwave irradiation has been developed. Its distinct advantages are short reaction times, good conversions and eco-friendly to methodology. The structures of these new Schiff bases were established by1H NMR, IR, MS spectra and elemental analysis.
- Shi, Yun,Peng, Yongle,Zhao, Zhigang,Li, Guohua,Li, Huarong
-
-
- Synthesis of novel arylhydrazide molecular tweezer artificial receptors based on deoxycholic acid using microwave irradiation
-
Eleven novel molecular tweezer anion receptors based on deoxycholic acid have been synthesised using microwave irradiation. Their structures were established by 1H NMR, IR, MS spectra and elemental analysis. Their binding properties were examined by UV-Vis spectra titration. The preliminary results indicate that these molecular tweezers show good recognition properties for H2PO4-, CH3COO- and NO3-.
- Li, Xiaorui,Zhao, Zhigang,Cheng, Yuyu,Li, Hui
-
p. 234 - 237
(2011/07/08)
-
- Preparation of novel molecular tweezers based on 3,6-O-(2- acylhydrazinocarbonyl) esters of hyodeoxycholic acid using microwave irradiation
-
Ten novel molecular tweezers based on the 3,6-O-(2-acylhydrazinocarbonyl) esters of hyodeoxycholic acid have been synthesised using microwave irradiation. Their structures were established by 1H NMR, IR, MS spectra and elemental analysis. Their binding properties were examined by UV-Vis spectra titration. The preliminary results indicate that these molecular tweezers show good recognition properties for Cl-, Br-, I-.
- Li, Xiaorui,Qiu, Liying,Mei, Qinggang,Bi, Qingwei,Zhao, Zhigang
-
p. 364 - 367
(2011/10/05)
-
- A new entry of amination reagents for heteroaromatic C-H bonds: Copper-catalyzed direct amination of azoles with chloroamines at room temperature
-
Chloroamine serves as an efficient amination reagent to the heteroaromatic C-H bond of azole under copper catalysis even at room temperature. This catalysis enables a rapid and concise construction of aminoazoles of great interest in biological and medicinal chemistry.
- Kawano, Tsuyoshi,Hirano, Koji,Satoh, Tetsuya,Miura, Masahiro
-
supporting information; experimental part
p. 6900 - 6901
(2010/07/05)
-
- Synthesis of novel triazole derivatives of methyl 3-oxocholanate using microwave irradiation
-
An efficient rapid method for the synthesis of new triazole derivatives derived from methyl 3-oxocholanate under microwave irradiation has been developed. These new compounds were characterised by 1H NMR, IR, ESI-MS spectra and elemental analyses. Some of these triazoles were tested for antibacterial activity against Staphylococcus aureus, Candida albicans and Escherichia coli.
- Yang, Jie,Cheng, YuYu,Shi, ZhiChuan,Zhao, ZhiGang
-
p. 680 - 683
(2011/04/26)
-
- Discovery of potent and selective inhibitors of human reticulocyte 15-lipoxygenase-1
-
There are a variety of lipoxygenases in the human body (hLO), each having a distinct role in cellular biology. Human reticulocyte 15-lipoxygenase-1 (15-hLO-1), which catalyzes the dioxygenation of 1,4-cis,cis-pentadiene- containing polyunsaturated fatty acids, is implicated in a number of diseases including cancer, atherosclerosis, and neurodegenerative conditions. Despite the potential therapeutic relevance of this target, few inhibitors have been reported that are both potent and selective. To this end, we have employed a quantitative high-throughput (qHTS) screen against ～74000 small molecules in search of reticulocyte 15-hLO-1 selective inhibitors. This screen led to the discovery of a novel chemotype for 15-hLO-1 inhibition, which displays nM potency and is >7500-fold selective against the related isozymes, 5-hLO, platelet 12-hLO, epithelial 15-hLO-2, ovine cyclooxygenase-1, and human cyclooxygenase-2. In addition, kinetic experiments were performed which indicate that this class of inhibitor is tight binding, reversible, and appears not to reduce the active-site ferric ion.
- Rai, Ganesha,Kenyon, Victor,Jadhav, Ajit,Schultz, Lena,Armstrong, Michelle,Jameson, J. Brian,Hoobler, Eric,Leister, William,Simeonov, Anton,Holman, Theodore R.,Maloney, David J.
-
scheme or table
p. 7392 - 7404
(2011/01/12)
-
- New potent inhibitors of tyrosinase: Novel clues to binding of 1,3,4-thiadiazole-2(3H)-thiones, 1,3,4-oxadiazole-2(3H)-thiones, 4-amino-1,2,4-triazole-5(4H)-thiones, and substituted hydrazides to the dicopper active site
-
A series of 1,3,4-thiadiazole-2(3H)-thiones, 1,3,4-oxadiazole-2(3H)-thiones, 4-amino-1,2,4-triazole-5(4H)-thiones, and substituted hydrazides were tailored and synthesized as new potent inhibitors of tyrosinase. The rationale for inhibitor design was based on the active site structural evidence from the crystal structures of bacterial tyrosinase and potato catechol oxidase enzymes. Kinetic and active site binding studies suggested mono-dentate binding of thiadiazole, oxadiazole, and triazole rings to the active site dicopper center of tyrosinase including hydrophobicity contributing to the potent inhibition. Kinetic plots showed mixed-type of inhibition by all 25 compounds. Substitutions at C3 of the triazole ring and C5 of the thiadiazole/oxadiazole rings were found to be playing a major role in the high binding affinity to tyrosinase. The current work may help develop new potent tyrosinase inhibitors against hyperpigmentation including potential insecticides.
- Ghani, Usman,Ullah, Nisar
-
scheme or table
p. 4042 - 4048
(2010/08/06)
-
- Design and synthesis of novel diphenic acid-based molecular tweezers
-
The design and synthesis of a new type of molecular tweezers is reported which have a 2,2′-diphenic acid backbone and two side chains that are attached to the backbone. This type of molecular tweezers has been to incorporate multiple hydrogen bonding groups into cleft to provide both orientation and selective complexation of substrate.
- Li, Weijie,Wang, Xiaoqing,Zhao, Zhigang,Han, Tao
-
experimental part
p. 106 - 108
(2010/06/19)
-
- Synthesis and structural characterisation of 2,4-bis(5-aryl-1,3,4-oxdiazol- 2-yl) pyridine derivatives
-
A convenient synthesis of 2,4-bis (5-aryl-1,3,4-oxdiazol-2-yl) derivatives of pyridine by the POCl3-mediated cyclodehydration of a variety of pyridine-2,4-dicarboxylic dihydrazides has been developed. The 20 novel intermediates and target molecules were characterised by IR, 1H NMR, MS and elemental analysis.
- Wang, Xiao Qing,Zhao, Zhi Gang,Liu, Xing Li,Li, Wei Jie
-
experimental part
p. 307 - 309
(2010/10/21)
-
- Design and synthesis of novel molecular tweezer anion receptors based on diphenic acid carbonyl thiosemicarbazide
-
Ten novel molecular tweezer anion receptors based on diphenic acid carbonyl thiosemicarbazide have been designed and synthesised in high yield and their binding properties were examined by UV-Vis spectra titration. Their structures were characterised by 1H NMR, IR, MS spectra and elemental analysis.
- Li, Xiaorui,Zhao, Zhigang,Li, Guohua,Shi, Peiyu
-
experimental part
p. 410 - 413
(2010/12/19)
-
- Synthesis, biological evaluation, and molecular docking studies of 2-chloropyridine derivatives possessing 1,3,4-oxadiazole moiety as potential antitumor agents
-
A series of new 2-chloropyridine derivatives possessing 1,3,4-oxadiazole moiety were synthesized. Antiproliferative assay results indicated that compounds 6o and 6u exhibited the most potent activity against gastric cancer cell SGC-7901, which was more potent than the positive control. Especially, compound 6o exhibited significant telomerase inhibitory activity (IC 50 = 2.3 ± 0.07 μM), which was comparable to the positive control ethidium bromide. Docking simulation was performed to position compound 6o into the active site of telomerase (3DU6) to determine the probable binding model.
- Zheng, Qing-Zhong,Zhang, Xiao-Min,Xu, Ying,Cheng, Kui,Jiao, Qing-Cai,Zhu, Hai-Liang
-
scheme or table
p. 7836 - 7841
(2011/01/13)
-
- BLUE LIGHT-EMITTING COMPOUND, METHOD FOR PRODUCING SAME AND LIGHT-EMITTING DEVICE UTILIZING SAME
-
The present invention provides blue-light emitting compounds capable of emitting blue light at a high luminance for a long time upon the application of electric energy, processes of producing the compounds, and luminescent elements including the blue light-emitting compounds. One of the compounds according to the present invention is characterized by the chemical structure represented by formula (1).
- -
-
Page/Page column 20-21
(2008/06/13)
-
- An efficient microwave-assisted one-pot conversion of carboxylic acids into hydrazides
-
A microwave-assisted protocol was developed to prepare hydrazides from corresponding carboxylic acids in good yields through transacylation with acethydrazide.
- Peng, Yanqing,Song, Gonghua
-
p. 768 - 769
(2007/10/03)
-
- Inhibition of advanced protein glycation by 8-quinolinecarboxylic hydrazide
-
Glycation of proteins is believed to be involved in the pathogenesis of diabetic complications, and thus the development of potent inhibitors of protein glycation is highly desirable. We tested the inhibitory effects of 12 hydrazide compounds against protein glycation and compared them with the effects of aminoguanidine (AG), a well-known inhibitor. When bovine serum albumin (BSA) was incubated with 100 mmol/l mannose for 10 days at 37°C in the presence and absence of hydrazide compounds or AG at 1 mmol/l, only p-anisic hydrazide inhibited Amadori product formation. On the other hand, 8 hydrazides as well as AG inhibited the formation of advanced glycation end products (AGEs). 8-Quinolinecarboxylic hydrazide (8-QCH), the most potent hydrazide, was more effective than AG. Neither 8-QCH nor AG affected the spontaneous decrease in Amadori products of preglycated BSA in the absence of sugar, but suppressed the spontaneous increase in AGEs from preglycated BSA, with higher potency of 8-QCH relative to AG. The results indicate that 8-QCH is a more potent inhibitor of AGE formation than AG and suggest that the inhibition mechanisms of 8-QCH and AG resemble each other.
- Miwa, Ichitomo,Tsugawa, Tohru,Koyasu, Katsuya,Terada, Yukimasa
-
p. 314 - 320
(2007/10/03)
-
