- Anti-androgens with full antagonistic activity toward human prostate tumor LNCaP cells with mutated androgen receptor
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Anti-androgens were designed based on the principle of inhibiting the folding of helix 12 of the nuclear androgen receptor. The prepared anti-androgens exhibited full antagonistic activity toward human prostate tumor LNCaP cells with T877A point-mutated nuclear androgen receptor, as far as examined, towards which other known anti-androgens, including hydroxyflutamide, are inactive or act as androgen agonists.
- Ishioka, Toshiyasu,Tanatani, Aya,Nagasawa, Kazuo,Hashimoto, Yuichi
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Read Online
- Biocatalytic Cross-Coupling of Aryl Halides with a Genetically Engineered Photosensitizer Artificial Dehalogenase
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Devising artificial photoenzymes for abiological bond-forming reactions is of high synthetic value but also a tremendous challenge. Disclosed herein is the first photobiocatalytic cross-coupling of aryl halides enabled by a designer artificial dehalogenase, which features a genetically encoded benzophenone chromophore and site-specifically modified synthetic NiII(bpy) cofactor with tunable proximity to streamline the dual catalysis. Transient absorption studies suggest the likelihood of energy transfer activation in the elementary organometallic event. This design strategy is viable to significantly expand the catalytic repertoire of artificial photoenzymes for useful organic transformations.
- Fu, Yu,Huang, Jian,Wu, Yuzhou,Liu, Xiaohong,Zhong, Fangrui,Wang, Jiangyun
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supporting information
p. 617 - 622
(2021/02/03)
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- Crystal-packing modes determine the solid-state ESIPT fluorescence in highly dipolar 2′-hydroxychalcones
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This work describes the systematic study of the structure-luminescence relationship of 15 hydroxy-chalcones directly in the crystal state. Chalcones are easily assembled at the gram scale allowing for efficient variation of their substitution motifs. Our molecule variants combine two modes of fluorescence generation, ESIPT and ICT, both known for their potential to achieve significant quantum yields even with emission in the red to near infrared, a region preferred for technologies as diverse as optoelectronics and chemical sensing. Quantum yields as high as 48% (at 665 nm) and emission wavelengths in the deep red region (710 nm, 5%) were achieved with variants equipped with a strained amino substituent in the donor portion (azetidinyl). Systematic XRD analysis of large monocrystals allowed for the identification of the subtle interplay of several inter- and intra-molecular parameters in achieving such performances, be it intramolecular planarity, non-classical H-bonds, and stacking modes.
- Bordy, Mathieu,Bretonnière, Yann,Hasserodt, Jens,Jeanneau, Erwann,Tordo, Alix
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supporting information
p. 12727 - 12731
(2021/10/06)
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- Dehydrogenation/(3+2) Cycloaddition of Saturated Aza-Heterocycles via Merging Organic Photoredox and Lewis Acid Catalysis
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Herein, we report a photoinduced dehydrogenation/(3+2) cycloaddition reaction by merging organic photoredox and Lewis acid catalysis, providing a straightforward and efficient approach for directly installing a benzofuran skeleton on the saturated aza-heterocycles. In this protocol, we also describe a novel organic photocatalyst (t-Bu-DCQ) with the advantages of a wider redox potential, easy synthesis, and a low price. Furthermore, the stepwise activation mechanism of dual C(sp3)-H bonds was demonstrated by a series of experimental and computational studies.
- Xiao, Teng-Fei,Zhang, Yi-Fan,Hou, Wen-Tao,Yan, Pen-Ji,Hai, Jun,Xu, Peng-Fei,Xu, Guo-Qiang
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supporting information
p. 8942 - 8946
(2021/11/24)
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- Pyridoxine-resveratrol hybrids as novel inhibitors of MAO-B with antioxidant and neuroprotective activities for the treatment of Parkinson's disease
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A series of pyridoxine-resveratrol hybrids were designed and synthesized as monoamine oxidase B inhibitors for the treatment of Parkinson's disease. Most of them exhibited potent inhibitory activities on MAO-B with high selectivity. Specifically, compounds 12a, 12g and 12l showed the most excellent inhibition to hMAO-B with the IC50 values of 0.01 μM, 0.01 μM and 0.02 μM, respectively. Further reversibility study demonstrated that 12a and 12l were reversible and 12g was irreversible MAO-B inhibitors. Molecular docking studies of MAO revealed the binding mode and high selectivity of these compounds with MAO-B. In addition, these three representative compounds also exhibited low cytotoxicity and excellent neuroprotective effect in the test on H2O2-induced PC-12 cell injury. Moreover, 12a, 12g and 12l showed good antioxidant activities and high blood-brain barrier permeability. Overall, all of these results highlighted 12a, 12g and 12l were potential and excellent MAO-B inhibitors for PD treatment.
- Cao, Zhongcheng,Deng, Yong,Li, Wei,Shi, Yichun,Song, Qing,Yang, Xia,Zhang, Li
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- Design, synthesis, characterization and fluorescence property evaluation of dehydroacetic acid-based chalcones
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Abstract: In this study, we decided to synthesize some new chalcone-type dyes derived from dehydroacetic acid (DHA) by the condensation of 4-amino-substituted benzaldehyde with DHA under the base-catalyzed condition and investigate their ability for rearrangement in acidic condition. For this purpose, initially we prepared the 4-aminobenzaldehyde derivatives via nucleophilic aromatic substitution reaction of 4-fluorobenzaldehyde with variety of amines in the presence of K2CO3 as base in DMF. The Knoevenagel condensation of DHA with 4-aminobenzaldehyde derivatives results in the desired compounds. In continuation, Fries rearrangement applied on DHA-chalcone compounds results in characterization of new pyranilidene-type derivatives. The optical responses of new dyes containing UV–Vis absorption and fluorescence spectroscopy were measured in dichloromethane (ET = 40?kcal/mol). Pyranilidene derivatives show low λmax values in comparison with chalcones, and molecule with strong dipole, in polar solvents, shows the bathochromic shift due to more stabilization of excited state in compared with ground state of molecule. Large stocks shifts were obtained for synthesized compounds. Graphic abstract: [Figure not available: see fulltext.].
- Teimuri-Mofrad, Reza,Rahimpour, Keshvar,Gholizadeh, Mohammad
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p. 1103 - 1109
(2019/12/30)
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- Multifunctional quinoxaline-hydrazone derivatives with acetylcholinesterase and monoamine oxidases inhibitory activities as potential agents against Alzheimer’s disease
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Multitarget molecules are considered as an effective way for the treatment of AD, instead of the classic one-drug-one-target strategy because of the multifactorial nature of AD. A variety of studies indicate that several enzymes inhibitors can be useful in the treatment of AD, including acetylcholinesterase (AchE), butyrylcholinesterase (BuChE) and monoamine oxidase (MAO). Various substituted quinoxaline-hydrazone derivatives were synthesized, and their activity in vitro were investigated, including AChE/BuChE inhibitory activity and MAOA/B inhibitory activity. Based on the experimental results, compound 5l exhibited good inhibitory potency on both AchE (IC50 = 0.028 ± 0.001 μM) and monoamine oxidase B (IC50 = 0.046 ± 0.002 μM). Molecular modeling studies showed that 5l could bind to the active site of AChE and MAO-B. Taken together, these results suggested that compound 5l might be a potential multifunctional agent for the treatment of AD.
- Ilgin, Sinem,Karaduman, Abdullah Burak,Levent, Serkan,Osmaniye, Derya,?avu?o?lu, Betül Kaya,?evik, Ulviye Acar,?zkay, Yusuf,Kaplancikli, Zafer As?m,Karaburun, Ahmet ?a?r?,Sa?lik, Begüm Nurpelin,Turan, Gülhan
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p. 1000 - 1011
(2020/04/29)
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- A two-aromatic substituted propylene ketone compound and its preparation method and application (by machine translation)
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The present invention discloses a two-aromatic substituted propylene ketone compound and its preparation method and application, its structural formula such as formula (I) as shown: Wherein A is B is hydrogen, methyl or ethyl; C is a substituted benzene ring, pyridine and furan heterocyclic, 2 - pyridyl, 3 - pyridyl, 4 - pyridyl, 5 - 1 H - indolyl, 4 - (N, N - dimethylamino) phenyl, 4 - (N - pyrrolyl) phenyl, 4 - [1 - (N - methyl piperazinyl)] phenyl or 4 - (1 - morpholinyl) phenyl. The compounds of the invention has a novel structure, to inhibit the cells MCL active effect, high safety, the preparation cost is low and the like, can be used as a MCL very promising drug. (by machine translation)
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Paragraph 0152; 0153; 0154; 0155; 0156
(2019/05/28)
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- Application of hydrazino and hydrazido linkers to connect benzenesulfonamides with hydrophilic/phobic tails for targeting the middle region of human carbonic anhydrases active site: Selective inhibitors of hCA IX
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Herein we report the design and synthesis of three different sets of novel benzenesulfonamides (5a-e, 7a-e and 10a-d) incorporating hydrophilic/hydrophobic tails by hydrazido or hydrazino linkers. The newly synthesized benzenesulfonamides were examined in vitro for their inhibitory activity towards four human (h) carbonic anhydrase (hCA, EC 4.2.1.1) isoforms, hCA I, II, IX and XII using a stopped-flow CO2 hydrase assay. All these isoforms were inhibited by the sulfonamides (5a-e, 7a-e and 10a-d) with variable degrees in the following KI ranges: 76.8–357.4 nM for hCA I, 8.2–94.6 nM for hCA II, 2.0–46.3 nM for hCA XI, and 8.3–88.3 nM for hCA XII. The sulfonamide 7d exhibited potent anti-proliferative activity against breast MCF-7 cancer cell line under both normoxic and hypoxic conditions with IC50 values equal 3.32 ± 0.06 and 8.53 ± 0.32 μM, respectively, which are comparable to the reference drug doxorubicin (IC50 = 2.36 ± 0.04 and 8.39 ± 0.25 μM, respectively). Furthermore, 7d was screened for cell cycle disturbance and apoptosis induction in MCF-7 cells. It was found to persuade cell cycle arrest at G2-M stage as well as to alter the Sub-G1 phase, also, 7d resulted in a significant increase in the percent of annexinV-FITC positive apoptotic cells from 1.03 to 18.54%. Molecular docking study was carried out for 7d within the hCA IX and hCA XII active sites to rationalize the obtained inhibition results.
- Allam, Heba Abdelrasheed,Fahim, Samar H.,F.Abo-Ashour, Mahmoud,Nocentini, Alessio,Elbakry, Mohamed E.,Abdelrahman, Mohamed A.,Eldehna, Wagdy M.,Ibrahim, Hany S.,Supuran, Claudiu T.
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p. 547 - 556
(2019/07/04)
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- Cu(II)-catalyzed C-N coupling of (hetero)aryl halides and N-Nucleophiles promoted by α-benzoin oxime
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We first reported the new application of a translate metal chelating ligand α-benzoin oxime for improving Cu-catalyzed C-N coupling reactions. The system could catalyse coupling reactions of (hetero)aryl halides with a wide of nucleophiles (e.g., azoles, piperidine, pyrrolidine and amino acids) in moderate to excellent yields. The protocol allows rapid access to the most common scaαolds found in FDA-approved pharmaceuticals.
- Yuan, Chunling,Zhang, Lei,Zhao, Yingdai
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- Methyl-α-d-glucopyranoside as Green Ligand for Selective Copper-Catalyzed N-Arylation
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In the selective N-arylation of amines or azoles with aryl halidesa-, methyl-α-d-glucopyranoside (MG) was found to function as a green ligand of copper powder. In addition, nitrogen heterocyclic amine compounds can also undergo the N-arylation coupling with heterocyclic aryl chlorides. This process allows access to a variety of aromatic amines and aryl azoles under mild reaction conditions, has good tolerance, and proceeds in moderate to high yield.
- Chen, Fengyang,Chen, Guoliang,Chen, Yuanguang,Du, Fangyu,Zhou, Qifan
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p. 4590 - 4600
(2019/12/11)
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- Design, synthesis and biological assessment of new thiazolylhydrazine derivatives as selective and reversible hMAO-A inhibitors
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In the recent works, it was shown that numerous thiazolylhydrazine derivatives display hMAO inhibitory activity in the range of micromolar concentration. Hence, in the present study a new series of new thiazole-hydrazines (3a-3n) were designed, synthesized, characterized and screened for their hMAO-A and hMAO-B inhibitory activity by an in vitro flurometric method. The enzyme inhibition assay revealed that most of the synthesized compounds have selective inhibition potency against hMAO-A. The compounds 3f and 3h showed promising hMAO-A inhibition with an IC50 values of 0.012 μM and 0.011 μM and significant selectivity indexes of 1214 and 1601 towards hMAO-A, respectively. The mechanism of hMAO-A inhibition of compounds 3f and 3h was investigated by Lineweaver-Burk graphics and reversible-competitive inhibition of hMAO-A was determined. Cytotoxicity and genotoxicity studies were carried out and the compound 3h was found as non-cytotoxic and non-genotoxic. Theoretical calculation of ADME properties suggested that synthesized compounds may have a good pharmacokinetic profile. The docking study of compound 3f and 3h revealed that there is a strong interaction between the active sites of hMAO-A and analyzed compound.
- Can, Nafiz ?ncü,Osmaniye, Derya,Levent, Serkan,Sa?l?k, Begüm Nurpelin,Korkut, Bü?ra,Atl?, ?zlem,?zkay, Yusuf,Kaplanc?kl?, Zafer As?m
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- Quantum yield improvement of red-light-emitting firefly luciferin analogues for in vivo bioluminescence imaging
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The dimethylamino group of AkaLumine ((4S)-2-[(1E,3E)-4-[4-(dimethylamino)phenyl]-1,3-butadien-1-yl]-4,5-dihydro-4-thiazolecarboxylic acid), a red-light-emitting firefly luciferin analogue, was replaced by cyclic amino groups (1-pyrrolidinyl, 1-piperidino, 1-azepanyl, and 4-morpholino) to give AkaLumine analogues exhibiting desirable bioluminescence with emission maxima in the red region (656–667 nm). In particular, a bioluminescence reaction of 1-pyrrolidinyl analogue with a recombinant Photinus pyralis luciferase showed a higher quantum yield than that with AkaLumine, giving an improved bioluminescence intensity. The 1-pyrrolidinyl analogue also showed the strongest luminescence in whole-body luciferase-expressing mice among the analogues, indicating that a quantum yield improvement of a luciferin analogue is effective to increase bioluminescence imaging intensity.
- Kiyama, Masahiro,Iwano, Satoshi,Otsuka, Satoshi,Lu, Shijia W.,Obata, Rika,Miyawaki, Atsushi,Hirano, Takashi,Maki, Shojiro A.
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p. 652 - 660
(2018/01/04)
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- Synthesis and anticandidal activity of new imidazole-chalcones
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In the present work, 15 new 1-(4-(1H-imidazol-1-yl)phenyl)-3-(4-substituedphenyl)prop-2-en-1-one derivatives (3a–3o) were synthesized to evaluate their antifungal activity. Structures of newly synthesized imidazole derivatives (3a–3o) were characterized by IR,1H-NMR,13C-NMR, and LCMSMS spectroscopic methods. The anticandidal activity of compounds (3a–3o) against C. albicans (ATCC 24433), C. krusei (ATCC 6258), C. parapsilosis (ATCC 22019), and C. glabrata (ATCC 90030) was elucidated according to the EUCAST definitive (EDef 7.1) method. Consistent with the activity studies, 3a–3d were found to be more potent derivatives with their MIC50 values (0.78 μg/mL–3.125 μg/mL) against Candida strains. Compound 3c indicated similar antifungal activity to ketoconazole against all Candida species and was evaluated as the most active derivative in the series. Effects of the most potent derivatives 3a–3d on ergosterol biosynthesis were observed by LC-MS-MS method, which is based on quantification of the ergosterol level in C. krusei. Moreover, these compounds were subjected to a cytotoxicity test for the preliminary toxicological profiles and were found as non-cytotoxic. Furthermore, docking studies for the most active derivative 3c were performed to evaluate its binding modes on lanosterol 14-α-demethylase. In addition to in vitro tests, docking studies also revealed that Compound 3c is a potential ergosterol biosynthesis inhibitor.
- Osmaniye, Derya,Avu?o Glu, Bet l Kaya,Sa gl?k, Beg m Nurpelin,Levent, Serkan,Acar evik, Ulviye,Atl?, Zlem,Zkay, Yusuf,Kaplanc?kl?, Zafer As?m
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- The Role of N-Substituents in Radiationless Deactivation of Aminated Derivatives of a Locked GFP Chromophore
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We report the creation of a novel group of the ABDI-BF2 fluorescent dyes based on the conformationally locked GFP chromophore. We studied the intramolecular mechanism of radiationless deactivation of the ABDI-BF2 fluorophore by introducing the various substituents at the nitrogen atom. The results of this study and our previous work allowed us to claim that in case of ABDI-BF2 this deactivation is determined by the formation of the nonfluorescent internal charge transfer exited state with a planar quinoidal structure. The electronic effects have a greater impact on the radiationless deactivation than the conformation. Thus, the introduction of an electron-donating group is more effective than the creation of rigid derivatives. The presented dyes are characterized by high fluorescence quantum yields and pH-independence in the physiological pH range, making them promising candidates for a wide spectrum of fluorescence labeling applications.
- Baleeva, Nadezhda S.,Zaitseva, Snezhana O.,Gorbachev, Dmitriy A.,Smirnov, Alexander Yu.,Zagudaylova, Marina B.,Baranov, Mikhail S.
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supporting information
p. 5219 - 5224
(2017/09/29)
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- Design, Synthesis, and Structure–Activity Relationship Analysis of Thiazolo[3,2-a]pyrimidine Derivatives with Anti-inflammatory Activity in Acute Lung Injury
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Acute lung injury (ALI) has a high lethality rate, and interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) contribute most to tissue deterioration in cases of ALI. In this study, we designed and synthesized a new series of thiazolo[3,2-a]pyrimidine derivatives based on a previously identified lead compound, and we evaluated their anti-inflammatory activities. Structure–activity relationship studies led to the discovery of two highly potent inhibitors. The two promising compounds were found to inhibit lipopolysaccharide (LPS)-induced IL-6 and TNF-α release in a dose-dependent manner in mouse primary peritoneal macrophages (MPMs). Furthermore, administration of these compounds resulted in lung histopathological improvements and attenuated LPS-induced ALI in vivo. Taken together, these data indicate that these novel thiazolo[3,2-a]pyrimidine derivatives could be developed as candidate drugs for the treatment of ALI.
- Chen, Lingfeng,Jin, Yiyi,Fu, Weitao,Xiao, Siyang,Feng, Chen,Fang, Bo,Gu, Yugui,Li, Chenglong,Zhao, Yunjie,Liu, Zhiguo,Liang, Guang
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supporting information
p. 1022 - 1032
(2017/07/11)
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- Synthesis of new donepezil analogues and investigation of their effects on cholinesterase enzymes
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Donepezil (DNP), an acetylcholinesterase (AChE) inhibitor, is one of the most preferred choices in Alzheimer diseases (AD) therapy. In the present study, 38 new DNP analogues were synthesized. Structures of the synthesized compounds (1–38) were elucidated by IR,1H NMR,13C NMR and HRMS spectroscopic methods and elemental analysis. Inhibitory potential of the compounds on cholinesterase enzymes was investigated. None of the compounds displayed significant activity on butyrylcholinesterase (BChE) enzyme. On the other hand, compounds 26–29 indicated important inhibitory activity on AChE enzyme. Kinetic studies were performed in order to observe the effects of the most active compounds on substrate-enzyme relationship. Cytotoxicity studies and theoretical calculation of pharmacokinetic properties were also carried out to get an information about toxicity and pharmacokinetic profiles of the compounds. The compounds 26–29 were found to be nontoxic at their effective concentrations against AChE. A good pharmacokinetic profile was predicted for these compounds. Docking studies were performed for the most active compounds 26–29 and interaction modes with enzyme active sites were determined. Docking studies revealed that there is a strong interaction between the active sites of AChE enzyme and analyzed compounds.
- Sa?l?k, Begüm Nurpelin,Ilg?n, Sinem,?zkay, Yusuf
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p. 1026 - 1040
(2016/11/09)
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- Asymmetrically Substituted and π-Conjugated 2,2′-Bipyridine Derivatives: Synthesis, Spectroscopy, Computation, and Crystallography
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A new series of monosubstituted styryl- and bistyryl-2,2′-bipyridine luminophores (compounds 16-23) have been synthesized via Horner-Wadsworth-Emmons reaction involving a monophosphonate and donor aromatic aldehydes. In the title chromophores, the amino donors are varied between acyclic and cyclic while the alkoxy donors are varied in terms of their number and position. The absorption maxima of these chromophores shift predominantly due to intramolecular charge transfer (ICT) between different donor and acceptor moieties. The title donor-acceptor molecules exhibit intense fluorescence in solution at room temperature, and their emissive behavior has been found to be highly sensitive to solvent polarity. The fluorescence spectra and quantum yields of all the chromophores were recorded in four different solvent media, and the chromophores 16, 17, 19, and 21 exhibit fluorescence in the solid state too. The influence of the nature and position of the donor functionalities in the conjugated backbone of the bipyridine moiety on the electronic absorption properties of the title chromophores (16-23) has been demonstrated, which has further been corroborated by DFT and TD-DFT computation both in gas phase and in solution phase. The crystal structure of compound 18 has been described as a representative member of the family (16-23).
- Bodapati, Ramakrishna,Sarma, Monima,Kanakati, Arunkumar,Das, Samar K.
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supporting information
p. 12482 - 12491
(2016/01/09)
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- Monocarboxylate transporter 1 inhibitors as potential anticancer agents
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Potent monocarboxylate transporter 1 inhibitors (MCT1) have been developed based on α-cyano-4-hydroxycinnamic acid template. Structure-activity relationship studies demonstrate that the introduction of p-N, N-dialkyl/diaryl, and o-methoxy groups into cyanocinnamic acid has maximal MCT1 inhibitory activity. Systemic toxicity studies in healthy ICR mice with few potent MCT1 inhibitors indicate normal body weight gains in treated animals. In vivo tumor growth inhibition studies in colorectal adenocarcinoma (WiDr cell line) in nude mice xenograft models establish that compound 27 exhibits single agent activity in inhibiting the tumor growth.
- Gurrapu, Shirisha,Jonnalagadda, Sravan K.,Alam, Mohammad A.,Nelson, Grady L.,Sneve, Mary G.,Drewes, Lester R.,Mereddy, Venkatram R.
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supporting information
p. 558 - 561
(2015/05/27)
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- Design, synthesis, 3D pharmacophore, QSAR, and docking studies of carboxylic acid derivatives as Histone Deacetylase inhibitors and cytotoxic agents
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In this study, five series of (E)-6-(4-substituted phenyl)-4-oxohex-5-enoic acids IIb-f (E), (E)-3-(4-(substituted)-phenyl)acrylic acids IIIa-g (E), 4-(4-(substituted)phenylamino)-4-oxobutanoic acids VIa,b,e, 5-(4-(substituted)phenylamino)-5-oxopentanoic acids VIIa,f and 2-[(4-(substituted)phenyl) carbamoyl]benzoic acids VIIIa,e were designed and synthesized. Selected compounds were screened in vitro for their cytotoxic effect on 60 human NCI tumor cell lines. Compound IIf (E) displayed significant inhibitory activity against NCI Non-Small Cell Lung A549/ATCC Cancer cell line (68% inhibition) and NCI-H460 Cancer cell line (66% inhibition). Moreover, the final compounds were evaluated in vitro for their cytotoxic activity on HepG2 Cancer cell line in which histone deacetylase (HDAC) is overexpressed. Compounds IIc (E), IIf (E), IIIb (E), and IIIg (E) exhibited the highest cytotoxic activity against HepG2 human cancer cell lines with IC50ranging from 2.27 to 10.71 μM. In addition, selected compounds were tested on histone deacetylase isoforms (HDAC1-11). Molecular docking simulation was also carried out for HDLP enzyme to investigate their HDAC binding affinity. In addition, generation of 3D-pharmacophore model and quantitative structure activity relationship (QSAR) models were combined to explore the structural requirements controlling the observed cytotoxic properties.
- Abdel-Atty, Mona M.,Farag, Nahla A.,Kassab, Shaymaa E.,Serya, Rabah A.T.,Abouzid, Khaled A.M.
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- Synthesis of 2-aryl-1,1-bis(silyl)alkenes containing alkyl(aryl)amine groups
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4-Alkyl-(aryl)aminobenzaldehydes have been generated via the nucleophilic aromatic substitution reaction of 4-fluorobenzaldehyde with appropriated amines and N-heterocycles using hexadecyltrimethylammonium bromide as catalyst and converted to 1,1-bis(silyl)-1-alkene derivatives via the Peterson olefination reaction. The reaction of (HMe2Si)3CLi with these aromatic aldehydes led to new 2-aryl-1,1-bis(silyl)alkenes.
- Safa, Kazem Dindar,Nadimi, Sanaz,Alyari, Maryam
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p. 498 - 501
(2014/11/08)
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- IMIDAZOTRIAZINONE COMPOUNDS
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The present invention provides imidazotriazinone compounds which are inhibitors of phosphodiesterase 9 and pharmaceutically acceptable salt thereof. The present invention further provides processes, pharmaceutical compositions, pharmaceutical preparations and pharmaceutical use of the compounds in the treatment of PDE9 associated diseases or disorders in mammals, including humans.
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Paragraph 0742; 0743; 0744
(2013/10/08)
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- Impact of reaction dynamics on synthesis of novel nitrogen containing aldehydes
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Impact of solvent dynamics, base employed and temperature conditions on the synthesis of novel Nitrogen containing aldehydes was studied. Piperazine, pyrrolidine and piperidine aldehydes were obtained in maximum yield and puritywith the K2CO3 base in presence of DMF solventand at 800 C temperatures.The synthesized compounds were characterized by IR, 1HNMR and MS Spectroscopy.
- Markandewar, Rajashree A.,Zia, Hanfi M.,Baseer
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p. 1531 - 1534
(2014/05/06)
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- Antimycobacterial activity evaluation, time-kill kinetic and 3D-QSAR study of C-(3-aminomethyl-cyclohexyl)-methylamine derivatives
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A series of C-(3-aminomethyl-cyclohexyl)-methylamine derivatives were synthesized and evaluated for their antitubercular activity. Some of the compounds exhibited potent activity against Mycobacterium tuberculosis H37Rv. One of the compound having t-butyl at para position of the benzene ring showed excellent activity even better than the standard drug ethambutol with MIC value 1.1 ± 0.2 μM. The time-kill kinetics study of two most active compounds showed rapid killing of the M. tuberculosis within 4 days. Additionally atom-based quantitative structure-activity relationship (QSAR) model was developed that gave a statistically satisfying result (R2) = 0.92, Q2 = 0.75, Pearson-R = 0.96 and effectively predicts the anti-tuberculosis activity of training and test set compounds.
- Kumar, Deepak,Raj, K. Kranthi,Bailey, Maiann,Alling, Torey,Parish, Tanya,Rawat, Diwan S.
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supporting information
p. 1365 - 1369
(2013/03/14)
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- Synthesis and evaluation of p-N,N-dialkyl substituted chalcones as anti-cancer agents
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Several new N,N-dialkyl substituted chalcones (chalconoids or benzylideneacetophenones) have been synthesized via the condensation of corresponding N,N-dialkylbenzaldehyde with various aryl methyl ketones. All the chalcones have been synthesized from readily available and cheap starting materials under environmentally benign conditions in very high yields without work up and column chromatographic purification. Synthesized compounds have been tested for their biological activity against pathogenic microorganisms such as Escherichia coli, Bacillus subtilis, and Mycobacterium smegmatis. Anti-cancer activity of these compounds has also been tested against multiple myeloma (RPMI-8226) and human mammary adenocarcinoma (MCF-7) cell lines. The most hydrophilic molecules 23 and 24 showed very good anti-cancer activity against MCF-7 cell lines at low micro-molar concentrations. All the compounds have also been evaluated for their activity against Beta-secretase 1 enzyme. One of the synthesized compounds showed Beta-secretase 1 enzyme inhibition activity at micro-molar concentration.
- Nelson, Grady,Alam, Mohammad A.,Atkinson, Tyler,Gurrapu, Shirisha,Sravan Kumar,Bicknese, Chris,Johnson, Joseph L.,Williams, Michael
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p. 4610 - 4614
(2013/09/23)
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- D-π-A-A-π-D prototype 2,2′-bipyridine dyads exhibiting large structure and environment-sensitive fluorescence: Synthesis, photophysics, and computation
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A series of 4,4′-π-conjugated-2,2′-bipyridine chromophores (MS 1-8) were synthesized, and their photophysical and thermal properties were investigated. The title "push-pull' chromophores", except MS 1, were integrated with both alkoxy and alkylamino donor functionalities that differ in their donation capabilities. The oligophenylenevinylene (OPV) chromophores MS 4-8 are associated with a π-extended backbone in which the position and the number of alkoxy donors were systematically varied. All of the studied systems possess a D-π-A-A-π-D dyad archetype in which the A-A is the central 2,2′-bipyridine acceptor core that is electronically attached with the donor termini through π-linkers. The fluorescence quantum yields of the synthesized chromophores are found to be sensitive to the molecular archetype and the solvent medium. Out of the eight fluorescent compounds reported in this article, the compound MS 5 exhibits fluorescence in the solid state also. The modulating effect of the nature, position, and number of donor functionalities on the optical properties of these classes of compounds has further been comprehended on the basis of DFT and TD-DFT computation in a solvent reaction field.
- Sarma, Monima,Chatterjee, Tanmay,Ghanta, Susanta,Das, Samar K.
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experimental part
p. 432 - 444
(2012/02/16)
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- Design, synthesis, and structure-activity relationship studies of 4-quinolinyl- and 9-acrydinylhydrazones as potent antimalarial agents
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Malaria is a major health problem in poverty-stricken regions where new antiparasitic drugs are urgently required at an affordable price. We report herein the design, synthesis, and biological investigation of novel antimalarial agents with low potential to develop resistance and structurally based on a highly conjugated scaffold. Starting from a new hit, the designed modifications were performed hypothesizing a specific interaction with free heme and generation of radical intermediates. This approach provided antimalarials with improved potency against chloroquine-resistant plasmodia over known drugs. A number of structure-activity relationship (SAR) trends were identified and among the analogues synthesized, the pyrrolidinylmethylarylidene and the imidazole derivatives 5r, 5t, and 8b were found as the most potent antimalarial agents of the new series. The mechanism of action of the novel compounds was investigated and their in vivo activity was assessed.
- Fattorusso, Caterina,Campiani, Giuseppe,Kukreja, Gagan,Persico, Marco,Butini, Stefania,Romano, Maria Pia,Altarelli, Maria,Ros, Sindu,Brindisi, Margherita,Savini, Luisa,Novellino, Ettore,Nacci, Vito,Fattorusso, Ernesto,Parapini, Silvia,Basilico, Nicoletta,Taramelli, Donatella,Yardley, Vanessa,Croft, Simon,Borriello, Marianna,Gemma, Sandra
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p. 1333 - 1343
(2008/09/20)
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- QUINOLIN-4-YLHYDRAZINE DERIVATIVES AS ANTIMALARIAL AGENT
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Novel quinolyl and acridinylhydrazone compounds of formula (I), which present remarkable biological activity especially against the choloroquine-resistant Plasmodium falciparum strains, useful for the treatment and prevention of malaria infection are described herein.
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Page/Page column 32
(2010/11/28)
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- Novel non-steroidal/non-anilide type androgen antagonists with an isoxazolone moiety
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3-Substituted (Z)-4-(4-N,N-dialkylaminophenylmethylene)-5(4H)-isoxazolones and related compounds were designed and prepared as candidates for structurally novel androgen antagonists. Several compounds showed potent anti-androgenic activity as assessed by nuclear androgen receptor binding assay and growth inhibition assay using androgen-dependent Shionogi carcinoma cells SC-3. They were approximately 10-220 times more potent than flutamide in these assay systems. They also showed anti-androgenic activity toward prostate tumor cell line LNCaP, which has an aberrant nuclear androgen receptor.
- Ishioka, Toshiyasu,Kubo, Asako,Koiso, Yukiko,Nagasawa, Kazuo,Itai, Akiko,Hashimoto, Yuichi
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p. 1555 - 1566
(2007/10/03)
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- Ultrasound effect on the synthesis of 4-alkyl-(aryl)aminobenzaldehydes
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The sonochemical nucleophilic aromatic substitutions on 4-fluorobenzaldehyde with different azacycloalkanes and azoles have been studied. A beneficial ultrasound effect was observed, reactions were clean and high yields of the products were isolated after 15 min sonication.
- Magdolen, Peter,Me?iarová, Mária,Toma, ?tefan
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p. 4781 - 4785
(2007/10/03)
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- ACTIVATING ACTION OF THE IMMONIUM GROUP IN THE SUBSTITUTION OF ALKOXYL AND HALOGEN ATOMS BY THE ALKYLAMINO GROUP IN THE BENZENE RING
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The substitution of the alkoxy group in o-, p-, and m-alkoxybenzylidenedimethylimmonium iodides by the action of aliphatic amines was investigated.Only p-alkoxy derivatives enter into the reaction forming, after hydrolysis, p-alkyl- and p-dialkylaminobenzaldehydes.Substitution can also be realized in p-alkoxybenzaldehydes and Schiff bases in the presence of the amine hydrochloride.Similarly, the halogen atom in p-halogenobenzaldehydes is substituted by the aliphatic amine residue.Quantum-mechanical calculations of the energy of anionic localization and charge at the attacked carbon atom o f the benzene ring are consistent with the experimantal data.
- Yudin, L. G.,Blokhin, A. V.,Bundel', Yu. G.,Simkin, B. Ya.,Terenin, V. I.
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p. 2064 - 2068
(2007/10/02)
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