- Design, synthesis and biological evaluation of novel pyrenyl derivatives as anticancer agents
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Polycyclic aromatic hydrocarbons are widespread in nature with a toxicity range from non-toxic to extremely toxic. A series of pyrenyl derivatives has been synthesized following a four-step strategy where the pyrene nucleus is attached with a basic heterocyclic moiety through a carbon linker. Virtual screening of the physicochemical properties and druggability has been carried out. The cytotoxicity of the compounds (1-8) have been evaluated in vitro against a small panel of human cancer cell lines which includes two liver cancer (HepG2 and Hepa 1-6), two colon cancer (HT-29 and Caco-2) and one each for cervical (HeLa) and breast (MCF-7) cancer cell lines. The IC50 data indicate that compound 6 and 8 are the most effective cytotoxic agents in the present set of pyrenyl derivatives, suggesting that having a 4-carbon linker is more effective than a 5-carbon linker and the presence of amide carbonyl groups in the linker severely reduces the efficacy of the compound. The compounds showed selectivity toward cancer cells at lower doses (51/4M) when compared with the normal hepatocytes. The mechanism of action supports the cell death through apoptosis in a caspase-independent manner without cleavage of poly (ADP-ribose) polymerase (PARP), even though the compounds cause plasma membrane morphological changes. The compounds, whether highly cytotoxic or mildly cytotoxic, localize to the membrane of cells. The compounds with either a piperidine ring (6) or an N-methyl piperazine (8) in the side chain were both capable of circumventing the drug resistance in SKOV3-MDR1-M6/6 ovarian cancer cells overexpressing P-glycoprotein. Qualitative structure-activity relationship has also been studied.
- Bandyopadhyay, Debasish,Sanchez, Jorge L.,Guerrero, Adrian M.,Chang, Fang-Mei,Granados, Jose C.,Short, John D.,Banik, Bimal K.
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- Deacetylative Amination of Acetyl Arenes and Alkanes with C-C Bond Cleavage
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The Br?nsted acid-catalyzed synthesis of primary amines from acetyl arenes and alkanes with C-C bond cleavage is described. Although the conversion from an acetyl group to amine has traditionally required multiple steps, the method described herein, which uses an oxime reagent as an amino group source, achieves the transformation directly via domino transoximation/Beckmann rearrangement/Pinner reaction. The method was also applied to the synthesis of γ-aminobutyric acids, such as baclophen and rolipram.
- Hyodo, Kengo,Hasegawa, Genna,Maki, Hiroya,Uchida, Kingo
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supporting information
p. 2818 - 2822
(2019/04/25)
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- Phototransformations of environmental contaminants in models of the aerosol: 2 and 4-Nitropyrene
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A comparative photochemical study of 2- and 4-nitropyrene (2- and 4-NO2Py) in different organic solvents was performed in order to provide information on the fate of these contaminants in models of the atmospheric aerosols. The isomers presented small photodegradation yields, 10?4–10?5 for 4-NO2Py and 10?5–10?6 for 2-NO2Py, demonstrating the low reactivity of the excited states and intermediate species that participate in their photodegradation. Photoproducts such as 4,5-pyrenedione, 4-hydroxypyrene, aminopyrene and pyrene were identified during the irradiation of 4-NO2Py. Substantial differences were observed in the photodegradation yields, and type and relative yields of the photoproducts of the 2-NO2Py and 4-NO2Py when compared to those of 1-NO2Py. These differences were related with the orientation of the nitro group and with differences in intersystem crossing rates which affect the yields of the pyrenoxy radical (PyO) and of the (π,π*) triplet state, principal precursors in their photodegradation. The smallest photodegradation yield was for 2-NO2Py due to the lack of interaction between the nitro group and the aromatic moiety thus resulting in a low yield of formation of the PyO radical. In the presence of O2, the photodegradation quantum yields of 4-NO2Py were reduced in all solvents due the quenching of the (π,π*) triplet state, and 4-aminopyrene was not observed thus demonstrating that its formation occurs from this state. These results suggest that in atmospheric aerosols containing an organic liquid-like layer, the nitropyrene isomers will show low photoreactivity resulting in an increase in their residence time in the atmosphere. An increase in reactivity is expected when the excited nitropyrenes are nearby substances with hydrogen donor capacities such as phenols. The photoproducts formed in the transformation could increase the toxicity of the particulate matter in the atmosphere.
- García-Berríos, Zulma I.,Arce, Rafael,Burgos-Martínez, Melanie,Burgos-Polanco, Natalia D.
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p. 131 - 140
(2016/09/07)
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- The K-Region in Pyrenes as a Key Position to Activate Aggregation-Induced Emission: Effects of Introducing Highly Twisted N,N-Dimethylamines
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A new design strategy to activate aggregation-induced emission (AIE) in pyrene chromophores is reported. In a previous report, we demonstrated that highly twisted N,N-dialkylamines of anthracene and naphthalene induce drastic AIE when these donors are introduced at appropriate positions to stabilize the S1/S0 minimum energy conical intersection (MECI). In the present study, this design strategy was applied to pyrene: the introduction of N,N-dimethylamine substituents at the 4,5-positions of pyrene, the so-called K-region, are likely to stabilize MECIs. To examine this hypothesis, four novel pyrene derivatives, which contain highly twisted N,N-dimethylamino groups at the 4- (4-Py), 4,5- (4,5-Py), 1- (1-Py), or 1,6-positions (1,6-Py) were tested. The nonradiative transitions of 4,5-Py are highly efficient (knr = 57.1 × 107 s-1), so that its fluorescence quantum yield in acetonitrile decreases to φfl = 0.04. The solid-state fluorescence of 4,5-Py is efficient (φfl = 0.49). In contrast, 1,6-Py features strong fluorescence (φfl = 0.48) with a slow nonradiative transition (knr = 11.0 × 107 s-1) that is subject to severe quenching (φfl = 0.03) in the solid state. These results underline that the chemistry of the pyrene K-region is intriguing, both from a photophysical perspective and with respect to materials science.
- Sasaki, Shunsuke,Suzuki, Satoshi,Igawa, Kazunobu,Morokuma, Keiji,Konishi, Gen-Ichi
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p. 6865 - 6873
(2017/07/17)
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- Encapsulation of Pd(II) into superparamagnetic nanoparticles grafted with EDTA and their catalytic activity towards reduction of nitroarenes and Suzuki-Miyaura coupling
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A robust, safe and magnetically recoverable palladium catalyst was synthesized by anchoring Pd(II) onto ethylenediaminetetraacetic acid-coated Fe3O4 (Fe3O4@EDTA) magnetic nanoparticles. The Fe3O4 magnetic nanoparticle-supported Pd(II)-EDTA complex catalyst thus obtained was characterized using scanning and transmission electron microscopies, thermogravimetric analysis, vibrating sample magnetometry, X-ray diffraction, and inductively coupled plasma atomic emission and Fourier transform infrared spectroscopies. Fe3O4@EDTA-Pd(II) was screened for the Suzuki reaction and reduction of nitro compounds in water. The Pd content of the catalyst was measured to be 0.28 mmol Pd g-1. In addition, the Fe3O4@EDTA-Pd catalyst can be easily separated and recovered with an external permanent magnet. The anchored solid catalyst can be recycled efficiently and reused five times with only a very slight loss of catalytic activity.
- Azizi, Kobra,Ghonchepour, Ehsan,Karimi, Meghdad,Heydari, Akbar
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p. 187 - 194
(2015/03/30)
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- Facile synthesis of biologically active heterocycles by indium-induced reactions of aromatic nitro compounds in aqueous ethanol
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Indium/ammonium chloride-induced reduction of aromatic nitro compounds to aromatic amines in aqueous ethanol was developed. Useful chemoselectivity was observed in the reduction reaction. This method was extended to reductive cyclization and rearrangement toward the synthesis of various biologically active heterocycles, including quinoline, oxazines, quinalonones, and phenanthridine in excellent yield. The oxophilicity of indium metal influenced the reaction in aqueous ethanol. Metals like zinc and tin were not effective in promoting this kind of reactions under the present environmentally friendly conditions.
- Banik, Bimal K.,Banik, Indrani,Samajdar, Susanta,Wilson, Mary
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p. 283 - 296
(2007/10/03)
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- Indium/ammonium chloride mediated selective reduction of aromatic nitro compounds: Practical synthesis of 6-aminochrysene
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Reduction of aromatic and heteroaromatic nitro compounds to the corresponding amino compounds was achieved by indium/ammonium chloride induced reaction in aqueous ethanol. This method was extended for the preparation of large quantities of 6-aminochrysene in excellent yield.
- Banik,Suhendra,Banik,Becker
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p. 3745 - 3754
(2007/10/03)
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