- Measurement of pH values in human tissues by two-photon microscopy
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pH values go live! A ratiometric two-photon (TP) probe (NP1, see scheme) that has a significant TP action cross-section, high photostability, negligible toxicity, and can estimate pH values in live cells and human tissues by two-photon microscopy is described. NP1 can detect the difference in pH between live cells from the gastroesophageal junction (GEJ) and the lower esophageal sphincter of patients with and without esophagitis (see image). Copyright
- Park, Hee Jung,Lim, Chang Su,Kim, Eun Sun,Han, Ji Hee,Lee, Tae Hee,Chun, Hoon Jai,Cho, Bong Rae
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- Stepwise dual stimuli triggered dual drug release by a single naphthalene based two-photon chromophore to reverse MDR for alkylating agents with dual surveillance in uncaging steps
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In this work, we depleted glutathione (GSH) by releasing SO2 with internal stimulus GSH itself, and also selectively marked the cancer cells followed by release of anticancer drug using another orthogonal stimulus i.e., two-photon (TP) NIR ligh
- Roy, Biswajit,Kundu, Moumita,Singh, Amit Kumar,Singha, Tara,Bhattacharya, Sayantan,Datta, Prasanta Kumar,Mandal, Mahitosh,Singh, N. D. Pradeep
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- Novel CLK1 inhibitors based on N-aryloxazol-2-amine skeleton - A possible way to dual VEGFR2 TK/CLK ligands
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Background Inhibitors of CLK protein kinases suppress cell growth and induce apoptosis by modulating pre-mRNA splicing in cancer. CLK family kinases are also involved in alternative splicing and RNA processing in Duchenne muscular dystrophy, Alzheimer's disease, HIV-1, and influenza virus. Small inhibitors are valuable tools for better understanding the molecular mechanisms of splicing and may serve as seeds for a novel class of therapeutics. Achievements Here we describe a discovery of four novel CLK1 inhibitors possessing N-aryloxazol-2-amine skeleton. Their activity against CLK1 (IC50: 20, 30, 40 and 80 nM) and some other CMGC kinases, predicted CLK binding poses, synthesis and physico-chemical characteristics are also stated. Additionally analysis of all PDB available CLK structures and interactions of their ligands was performed. There are only few powerful dual CLK/VEGFR inhibitors known in the literature. We proposed that our inhibitors have similar binding places and interactions in CLK1, 3 and VEGFR2 TK mostly due to the joint N-aryloxazol-2-amine pharmacophoric fragment. One of our N-aryloxazol-2-amines already proved a good activity against both VEGFR2 and CLK1 enzymes (23/80 nM, resp). We proposed that the presented class of compounds has a potential to be developed in dual VEGFR2/CLK clinical compounds with prospective synergy to treat cancer.
- Murár, Miroslav,Dobia?, Juraj,?ramel, Peter,Addová, Gabriela,Hanquet, Gilles,Bohá?, Andrej
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- Usnic Acid Enaminone-Coupled 1,2,3-Triazoles as Antibacterial and Antitubercular Agents
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(+)-Usnic acid, a product of secondary metabolism in lichens, has displayed a broad range of biological properties such as antitumor, antimicrobial, antiviral, anti-inflammatory, and insecticidal activities. Interested by these pharmacological activities and to tap into its potential, we herein present the synthesis and biological evaluation of new usnic acid enaminone-conjugated 1,2,3-triazoles 10-44 as antimycobacterial agents. (+)-Usnic acid was condensed with propargyl amine to give usnic acid enaminone 8 with a terminal ethynyl moiety. It was further reacted with various azides A1-A35 under copper catalysis to give triazoles 10-44 in good yields. Among the synthesized compounds, saccharin derivative 36 proved to be the most active analogue, inhibiting Mycobacterium tuberculosis (Mtb) at an MIC value of 2.5 μM. Analogues 16 and 27, with 3,4-difluorophenacyl and 2-acylnaphthalene units, respectively, inhibited Mtb at MIC values of 5.4 and 5.3 μM, respectively. Among the tested Gram-positive and Gram-negative bacteria, the new derivatives were active on Bacillus subtilis, with compounds 18 [3-(trifluoromethyl)phenacyl] and 29 (N-acylmorpholinyl) showing inhibitory concentrations of 41 and 90.7 μM, respectively, while they were inactive on the other tested bacterial strains. Overall, the study presented here is useful for converting natural (+)-usnic acid into antitubercular and antibacterial agents via incorporation of enaminone and 1,2,3-triazole functionalities.
- Bangalore, Pavan K.,Vagolu, Siva K.,Bollikanda, Rakesh K.,Veeragoni, Dileep K.,Choudante, Pallavi C.,Misra, Sunil,Sriram, Dharmarajan,Sridhar, Balasubramanian,Kantevari, Srinivas
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supporting information
p. 26 - 35
(2020/01/03)
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- VIOLET LASER EXCITABLE DYES AND THEIR METHOD OF USE
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The present invention provides dye compounds optimally excited at about 400 nm and have a Stokes shift of at least about 80 nm. These dyes find use in detection of analyte in a sample and the preparation of dye-conjugates.
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Paragraph 0239
(2016/12/22)
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- Synthesis and evaluation of 2-(2-arylmorpholino)ethyl esters of ibuprofen hydrochlorides as COX-2 and serotonin reuptake inhibitors
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Based on the positive effects of COX-2 inhibitors on depressive symptoms and the desirable physicochemical and biological properties of the morpholine group, a series of novel 2-(2-arylmorpholino)ethyl esters of ibuprofen hydrochlorides were designed, synthesized, and tested for their COX-2 inhibitory and serotonin reuptake inhibitory activities in vitro. The structure-activity relationships of the 2-(2-arylmorpholino)ethyl esters of ibuprofen hydrochlorides as dual COX-2 and serotonin reuptake inhibitors were determined and discussed in detail. The biological assays indicated that five of the compounds possess good COX-2 selectivity (selectivity index COX-1/COX-2 42.8-158.1). The compound 2-[2-(4-benzyloxyphenyl)morpholino]ethyl 2-(4-iso-butylphenyl)-propanoate hydrochloride (1k) shows better COX-2 inhibitory activity (IC50 = 0.78 μM) than ibuprofen (IC 50 = 7.6 μM), and it simultaneously possesses favorable serotonin reuptake inhibitory activity. A series of novel 2-(2-arylmorpholino)ethyl esters of ibuprofen were tested for their COX-2 inhibitory and serotonin reuptake inhibitory activities in vitro. Most of the compounds possess good COX-2 selectivity. Compound 1k shows better COX-2 inhibitory activity than ibuprofen and possesses favorable serotonin reuptake inhibitory activity. According to the results of the biological assays, 2-arylmorpholine-substituted ibuprofen could be used as a core structure to design novel dual COX-2 and serotonin reuptake inhibitors.
- Dou, Jie,Shi, Lei,Hu, Aixi,Dong, Minyu,Xu, Jiangping,Liu, Ailin,Jiang, Yiping
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- One-pot preparation of arylethynyl sulfides and bis(arylethynyl) sulfides
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An efficient preparation for arylethynyl sulfides 1 and bis(arylethynyl) sulfides 2 has been accomplished through a one-pot, three-step strategy that starts from arylethanonyl sulfides and bis(arylethanonyl) sulfides, respectively, without the use of various terminal arylacetylenes as substrates. When lithium hexamethyldisilazane (LHMDS), ClP(O)(OEt)2, and LHMDS were sequentially added to a tetrahydrofuran solution of different substrates [arylethanonyl sulfides or bis(arylethanonyl) sulfides], 1 or 2 were obtained in moderate to good yields. The reaction procedure involves the formation of an enol phosphate and a subsequent base-induced elimination. An efficient preparation of arylethynyl sulfides 1 and bis(arylethynyl) sulfides 2 has been accomplished by a one-pot, three-step strategy that starts from arylethanonyl sulfides and bis(arylethanonyl) sulfides, respectively, to give 1 and 2 in moderate to good yields. The reaction mechanism involves the formation of an enol phosphate that undergoes a subsequent base-induced elimination. Copyright
- Su, Qiong,Zhao, Zi-Jian,Xu, Feng,Lou, Peng-Cai,Zhang, Kai,Xie, De-Xun,Shi, Lei,Cai, Qing-Yun,Peng, Zhi-Hong,An, De-Lie
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supporting information
p. 1551 - 1557
(2013/04/23)
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- Novel synthetic approach toward C-substituted piperazine derivatives via C-N bonds formation of α-bromoarylethanones and ethanolamine
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A new method for the synthesis of novel C-substituted piperazine derivatives bearing aryl substituents on 2,6-C positions has been developed by one-pot three-component sequential reaction of α-bromoarylethanones with ethanolamine in the presence of formic
- Cao, Gao,Hu, Ai-Xi,Xie, Yan-Li,Zhou, Zhen
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p. E126-E130
(2013/06/04)
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- Design, synthesis and biological evaluation of 2-(2-aryl-morpholino-4-yl) ethyl esters of indomethacin as potential cyclooxygenase-2 (COX-2) inhibitors
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A number of novel 2-(2-arylmorpholino-4-yl)ethyl 1-(4-chlorobenzoyl)-5- methoxy-2-methyl-1H-indol-3-acetate hydrochlorides were synthesized and tested for their cyclooxygenase (COX-1 and COX-2) inhibition properties in vitro. Many of these compounds exhibited moderate to good selective COX-2 inhibition, and subtle structural changes in the substituents on the side chain of the ester moiety altered the inhibitory properties significantly. 2-[2-(4-Butoxyphenyl) morpholino-4-yl]ethyl 1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-acetate hydrochloride (1f), showed good selective COX-2 inhibitory activity (Selective index (SI) 182), which is comparative with celecoxib (SI 214), a COX-2 inhibitor of diarylpyrazoles. While 2-[2-(2,4-dichloro-5-fluorophenyl)morpholino-4-yl] ethyl 1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-acetate hydrochloride (1g), showed greater selective COX-2 inhibitory activity (SI 358) than celecoxib. Both compounds were identified as compromising derivatives in this class to reduce the side effects generated by nonsteroidal anti-inflammatory drugs (NSAIDs) indomethacin.
- Shi, Lei,Hu, Aixi,Xu, Jiangping,Jiang, Yiping
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scheme or table
p. 1339 - 1344
(2012/08/29)
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- Solvent free synthesis, spectral studies and antioxidant activities of some 6-substituted ω-bromo-2-naphthyl ketones and their esters
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A series of 6-substituted ω-bromo-2-naphthyl ketones and 6-substituted 2-naphthacyl esters have been synthesized by greener synthetic method using fly-ash:water catalyzed aqueous phase reaction. These ketones and esters have been characterized by their physical constants, GC-MS, IR and NMR spectral data. These compounds exist as two rotomers and the carbonyl frequencies of these rotomers have been assigned and correlated with Hammett substituent constants, F, R and Swain-Lupton's parameters. The antioxidant activities of the synthesized esters have been evaluated.
- Thirunarayanan,Vanangamudi,Sathiyendran,Ravi
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experimental part
p. 593 - 604
(2011/06/21)
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- Design of more potent squalene synthase inhibitors with multiple activities
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With the increasing realization that modulating a multiplicity of targets can be an asset in the treatment of multifactorial disorders, we hereby report the synthesis and evaluation of the first compounds in which antioxidant, anti-inflammatory as well as squalene synthase (SQS) inhibitory activities are combined by design, in a series of simple molecules, extending their potential range of activities against the multifactorial disease of atherosclerosis. The activity of the initially synthesized antihyperlipidemic morpholine derivatives (1-6), in which we combined several pharmacophore moieties, was evaluated in vitro (antioxidant, inhibition of SQS and lipoxygenase) and in vivo (anti-dyslipidemic and anti-inflammatory effect). We further compared the in vitro SQS inhibitory action of these derivatives with theoretically derived molecular interactions by performing an in silico docking study using the X-ray crystal structure of human SQS. Based on low energy preferred binding modes, we designed potentially more potent SQS ligands. We proceeded with synthesizing and evaluating these new structures (7-12) in vitro and in vivo, to show that the new derivatives were significantly more active than formerly developed congeners, both as SQS inhibitors (20-70-fold increase in activity) and antioxidants (4-30-fold increase in activity). A significant correlation between experimental activity [Log(1/IC50)] and the corresponding binding free energy (ΔGb) of the docked compounds was shown. These results, taken together, show a promising alternative and novel approach for the design and development of multifunctional antiatherosclerosis agents.
- Kourounakis, Angeliki P.,Matralis, Alexios N.,Nikitakis, Anastasios
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experimental part
p. 7402 - 7412
(2010/12/25)
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- Photochemical α-bromination of ketones using N-bromosuccinimide: a simple, mild and efficient method
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Aromatic and aliphatic carbonyl compounds undergo facile bromination with N-bromosuccinimide under UV-vis irradiation to give the corresponding α-brominated ketones in good yields, at low temperatures (30 °C), without any catalyst, catalyst support or radical initiator and within a short time.
- Arbuj, Sudhir S.,Waghmode, Suresh B.,Ramaswamy
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p. 1411 - 1415
(2007/10/03)
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- Thiazolo-naphthyl acids
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The present invention relates to thiazolo-naphthyl acids of the formula and methods of using them to modulate PAI-1 expression and to treat PAI-1 related disorders.
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Page/Page column 13-14
(2008/06/13)
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- PYRROLO-NAPHTHYL ACIDS AS PAI-1 INHIBITORS
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The present invention relates to pyrrolo-naphthyl compounds of the formula and methods of using them to modulate PAI-1 expression and to treat PAI-1 related disorders.
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Page/Page column 29
(2010/10/20)
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- OXAZOLO-NAPHTHYL ACIDS AS PLAMINOGEN ACTIVATOR INHIBTOR TYPE-1 (PAI-1) MODULATORS USEFUL IN THE TREATMENT OF THROMBOSIS AND CARDIOVASCULAR DISEASES
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The present invention relates to oxazolo-naphthyl acids of the formula (I) and methods of using them to modulate PAI-1 expression and to treat PAI-1 related disorders.
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Page/Page column 32
(2010/10/20)
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- LES TRIBROMURES DE PHOSPHONIUMS. AGENTS DE BROMINATION DE SUBSTRATS ORGANIQUES
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The reactivities and selectivities of phosphonium tribromides 1-4 towards ketones and their ketals, in the presence of other functional group reactive toward bromide (free enolic position, activated aromatic ring or double bond), are studied and compared with the trimethyl phenyl ammonium tribromide 5.The abilities of the two kinds of tribromides are similar, with a better selectivity of phosphonium salts toward unsaturated ketones, which is probably induced by the greater stability of the ion-pair in phosphonium salts.They act essentially by the tribromide without specific bond interactions between phosphorus and heteroatom of the substrate.
- Cristau, Henri-Jean,Torreilles, Eliane,Morand, Philippe,Christol, Henri
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p. 357 - 368
(2007/10/02)
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- 1-(Naphthylalkyl)-1H-imidazole derivatives, a new class of anticonvulsant agents
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Potent anticonvulsant activity has been demonstrated for a large number of 1-(naphthylalkyl)-1H-imidazoles containing a variety of functional groups in the alkylene bridge. The presence of a small oxygen function in the bridge, in general, confers a high
- Walker,Wallach,Hirschfeld
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