- Synthesis and mechanistic studies of quinolin-chlorobenzothioate derivatives with proteasome inhibitory activity in pancreatic cancer cell lines
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Inhibition of proteasome activity blocks the degradation of dysfunctional proteins and induces cancer cell death due to cellular stress. Thus, proteasome inhibitors represent an attractive class of anticancer agents, and bortezomib, carfilzomib and ixazomib have been FDA-approved to treat multiple myeloma. However, cancer cells acquire resistance to these inhibitors through point mutations in the proteasome catalytic subunit or induction of alternative compensatory mechanisms. In this study, we identified a quinolin-chlorobenzothioate, QCBT7, as a new proteasome inhibitor showing cytotoxicity in a panel of cancer cell lines. QCBT7 is a more stable derivative of quinoline-8-thiol that targets the regulatory subunit instead of the catalytic subunit of the proteasome. QCBT7 caused the accumulation of ubiquitylated proteins in the cancer cells, indicating its proteasome inhibitory activity. Additionally, QCBT7 increased the expression of a set of genes (PFKFB4, CHOP, HMOX1 and SLC7A11) at both nascent RNA and protein levels, similarly to the known proteasome inhibitors MG132 and ixazomib. Together, QCBT7 induces proteasome inhibition, hypoxic response, endoplasmic reticulum stress and glycolysis, finally leading to cell death. Importantly, we have identified PFKFB4 as a potential biomarker of proteasome inhibitors that can be used to monitor treatment response.
- Hu, Shuai,Jin, Yi,Liu, Yanghan,Ljungman, Mats,Neamati, Nouri
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p. 884 - 895
(2018/09/29)
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- From Surprising Solvothermal Reaction to Uncommon Zinc(II)-Catalyzed Aromatic C-H Activation Reaction for Direct Nitroquinoline Synthesis
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In this work, we first found a surprising solvothermal reaction for direct dinitration of quinoline derivative. To explore the application in direct nitroquinoline synthesis, this reaction was subsequently modified as an equivalent reaction in a Schlenk tube. More significantly, after a constant attempt, nitrated derivative was obtained in optimized condition with a zinc(II) sulfate catalyst, where some substrates with strong electron-withdrawing group were first nitrated by a directly catalyzed condition. This new zinc(II)-catalyzed aromatic C-H activation reaction is the first example of direct dinitration by a single catalyst, which will be a new facile and environmentally friendly strategy to access synthetically useful nitroquinoline derivative.
- Wang, Yazhen,Yu, Feihu,Han, Xiao,Li, Ming,Tong, Yue,Ding, Jie,Hou, Hongwei
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supporting information
p. 5953 - 5958
(2017/05/22)
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- Directing-group-assisted copper-catalyzed oxidative esterification of phenols with aldehydes
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A directing-group-assisted copper-catalyzed oxidative esterification of phenols with aldehydes using TBHP as an oxidant was described. This methodology which showed the advantages of base, ligand free, short routes and functional group tolerance could be used as an alternative protocol for the classical esterification reactions.
- Zheng, Yong,Song, Wei-Bin,Xuan, Li-Jiang
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p. 10834 - 10843
(2015/11/17)
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- Solid-Phase Benzoylation of Phenols and Alcohols in Microwave Reactor: An Ecofriendly Protocol
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An efficient solid-phase benzoylation of phenols and alcohols was developed under microwave irradiation. A stoichiometric amount of benzoyl chloride was sufficient to carry out the reaction. This benzoylation features short reaction time, good yields, and easy workup procedures. Furthermore, the scope of the reaction was extended to prepare 3,5-dinitrobenzoyl derivatives of alcohols.
- Chakraborty, Suchandra,Saha, Ahana,Basu, Kaushik,Saha, Chandan
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supporting information
p. 2331 - 2343
(2015/10/12)
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- Copper-mediated ortho-nitration of (hetero)arenecarboxylates
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Various (hetero)arenecarboxylic acids were converted to the corresponding Daugulis amides and nitrated selectively in the ortho-position in the presence of [CuNO3(PPh3)2] and AgNO2 at 50 °C. A microwave-assisted saponification allows regenerating the carboxylate group within minutes, which may then be removed tracelessly by protodecarboxylation, or substituted by aryl- or alkoxy-groups via decarboxylative cross-coupling.
- Katayev, Dmitry,Pfister, Kai F.,Wendling, Timo,Goossen, Lukas J.
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supporting information
p. 9902 - 9905
(2014/08/18)
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- NMR study of O and N, O-substituted 8-quinolinol derivatives
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The 1H and 13C NMR spectral study of several biologically active derivatives of 8-quinolinol have been made through extensive NMR studies including homodecoupling and 2D-NMR experiments such as COSY-45°, NOESY, and HeteroCOSY. Electron donating resonance and electron withdrawing inductive effect of several groups showed marked changes in chemical shifts of nuclei at the seventh positions of O-substituted quinolinols (2-15). Although in N-alkyl, 8-alkoxyquinolinium halides (16-21), ring A rightly showed low frequency chemical shift values. Copyright
- Mastoor, Sobia,Faizi, Shaheen,Saleem, Rubeena,Siddiqui, Bina Shaheen
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p. 115 - 121
(2014/03/21)
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- Subtype-selectivity of metal-dependent methionine aminopeptidase inhibitors
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Inhibitors of methionine aminopeptidases (MetAPs) are treatment options for various pathological conditions. Several inhibitor classes have been described previously, but only few data on the subtype selectivity, which is of crucial importance for these enzymes, is available. We present a systematic study on the subtype- and species-selectivity of MetAP inhibitors that require the binding of an auxiliary metal ion. This includes, in particular, compounds based on the benzimidazole pharmacophore, but also hydroxyquinoline and picolinic acid derivatives. Our data indicates that a significant degree of selectivity can be attained with metal-dependent MetAP inhibitors.
- Altmeyer, Markus A.,Marschner, Aline,Schiffmann, Rolf,Klein, Christian D.
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supporting information; experimental part
p. 4038 - 4044
(2010/08/20)
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- 8-Hydroxyquinoline benzoates as highly sensitive fluorescent chemosensors for transition metal ions
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(Graph Presented) 8-Hydroxyquinoline benzoates were developed as a new set of 8-HQ derivatives for highly sensitive fluorescent chemosensors for transition metal ions. A prominent fluorescence enhancement was found in the presence of transition metal ions such as Hg2+ and Cu2+, and this was suggested to result from the suppression of radiationless transitions from the nπ* state in the chemosensors.
- Zhang, Han,Han, Li-Feng,Zachariasse, Klaas A.,Jiang, Yun-Bao
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p. 4217 - 4220
(2007/10/03)
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- In vitro studies of the antibacterial and antifungal activity of oxime and its derivatives
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Twenty-one derivatives of 8-hydroxyquinoline (oxine, 8H, CAS 148-24-3) were prepared and characterized by UV, IR, MS and NMR spectroscopy. Four of these derivatives, N-butyl, 8-butyloxyquinolinium bromide (HBD), 8-pentyloxyquinoline (HPEM), N-pentyl, 8-pentyloxyquinolinium bromide (HPED) and N-benzyl, 8-benzyloxy quinolinium chloride (HBED) are new and reported for the first time. The antimicrobial activity of these compounds was carried out in vitro against 11 Gram positive and 18 Gram negative bacteria, and 18 fungi including 9 dermatophytes, 7 other filamentous fungi and 2 Candida species. Three compounds namely, HPRD, HPED and HBED were found to possess significant antibacterial activity in order of HPED > HPRD > HBED, whereas 4 were found to possess significant antifungal activity in order of 8H > HT > HPEM > 8B.
- Khan,Ahmed Khan,Khalid,Ahmed,Siddiqui,Saleem,Siddiqui,Faizi
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p. 972 - 975
(2007/10/02)
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