The solar-chemical photo-Friedel–Crafts heteroacylation of 1,4-quinones

Benites, Julio; Ríos, David; Diaz, Pilar; Valderrama, Jaime A.

doi:10.1016/j.tetlet.2010.11.149

Cited by 37 publications

(31 citation statements)

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“…The differences in the EC 50 -values indicated that the nature of the substituent group influences the cytotoxicity of these quinones. A previous study showed that changes in the quinoid core alter the cytotoxicity of quinones in a panel of cancer cells (MCF7, DU145, T24, J82, AGS, and BEM-SK-1) and impair the proliferative capacity of T24 cells (12). Additionally, the electronic properties of the substituent bound to the quinone core may interfere with the redox cycling process and thus affect the production of ROS (11).…”

Section: Resultsmentioning

confidence: 99%

“…General procedure for the preparation of 3-acyl-2-phenylamino-1,4-naphthoquinones. The preparation of the core 3-acyl-2-phenylamino-1,4-naphthoquinones was initiated with the synthesis of 2-acylnaphthohydroquinones via solar-induced Photo-Friedel-Crafts acylation of 1,4-naphthoquinone with aldehydes according to a previously reported procedure (12). The resulting compounds were then oxidized with silver (I) oxide in dichloromethane, and the corresponding 2-acyl-1,4-naphthoquinones were reacted in situ with selected phenylamines in a one-step procedure to produce the corresponding 3-acyl-2-phenylamino-1,4-naphthoquinones DPB1-DPB9 ( Fig.…”

Section: Methodsmentioning

confidence: 99%

“…The redox properties of the radical anion species enable these compounds to undergo a catalytic cycle and in the presence of molecular oxygen they generate reactive oxygen Substituted 3-acyl-2-phenylamino-1,4-naphthoquinones intercalate into DNA and cause genotoxicity through the increased generation of reactive oxygen species culminating in cell death species (ROS), including hydrogen peroxide and superoxide anions, which damage the DNA and certain essential proteins. These agents represent a promising approach for targeting cancer cells (10)(11)(12). Indeed, as a result of metabolic changes and oncogene activation, cancer cells generally exhibit high levels of ROS, which can stimulate cell proliferation and promote genetic instability (13).…”

Section: Introductionmentioning

confidence: 99%

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Substituted 3-acyl-2-phenylamino-1,4-naphthoquinones intercalate into DNA and cause genotoxicity through the increased generation of reactive oxygen species culminating in cell death

Farias

Pich²,

Kviecinski

et al. 2014

Molecular Medicine Reports

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Naphthoquinones interact with biological systems by generating reactive oxygen species (ROS) that can damage cancer cells. The cytotoxicity and the antitumor activity of 3‑acyl‑2‑phenylamino‑1,4‑naphthoquinones (DPB1‑DPB9) were evaluated in the MCF7 human breast cancer cell line and in male Ehrlich tumor‑bearing Balb/c mice. DPB4 was the most cytotoxic derivative against MCF7 cells (EC50 15 µM) and DPB6 was the least cytotoxic one (EC50 56 µM). The 1,4‑naphthoquinone derivatives were able to cause DNA damage and promote DNA fragmentation as shown by the plasmid DNA cleavage assay (FII form). In addition, 1,4‑naphthoquinone derivatives possibly interacted with DNA as intercalating agents, which was demonstrated by the changes caused in the fluorescence of the DNA‑ethidium bromide complexes. Cell death of MCF7 cells induced by 3‑acyl‑2‑phenylamino‑1,4‑naphthoquinones was mostly due to apoptosis. The DNA fragmentation and subsequent apoptosis may be correlated to the redox potential of the 1,4‑naphthoquinone derivatives that, once present in the cell nucleus, led to the increased generation of ROS. Finally, certain 1,4‑naphthoquinone derivatives and particularly DPB4 significantly inhibited the growth of Ehrlich ascites tumors in mice (73%).

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Substituted 3-acyl-2-phenylamino-1,4-naphthoquinones intercalate into DNA and cause genotoxicity through the increased generation of reactive oxygen species culminating in cell death

Farias

Pich²,

Kviecinski

et al. 2014

Molecular Medicine Reports

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“…8 In order to explore greener conditions to prepare 2 from naphthoquinone 1 and furfural by avoiding the use of the toxic solvent benzene, a series of photoacylation experiments were run in environmentally benign solvent media. According to the Pfizer solvent selection guide, 9,10 the following "preferred" solvent were selected: water, Herein we wish to report results on the synthesis of acylhydroquinone 2 by photoacylation of 1,4-naphthoquinone 1 with furfural by using solar irradiation in different green solvent media.…”

Section: Photoacylation Of 14-naphthoquinone 1 With Furfural In Greementioning

confidence: 99%

Green Synthetic Approaches to Furoylnaphthohydroquinone and Juglone

Benites

Michael

Luis

et al. 2014

J. Chil. Chem. Soc.

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The synthesis of two valuable precursors of biological active compounds named 2-(furan-2-yl)-1,4-dihydroxynapthohydroquinone 2 and 5-hydroxy-1,4-naphthoquinone (4, juglone) via solar photo-induced reactions from 1,4-naphthoquinone 1 and 1,5-dihydroxynaphthalene 3 in green solvent media is reported. When t-butyl alcohol and the binary t-ButOH/DMK and ternary i-PrOAc/DMK/MEK solvent mixtures were used, acylhydroquinone 2 was isolated in yields of 80, 83 and 77%, respectively. The sensitized photooxygenation of 3 "on water" and in water containing sodium dodecyl sulfate produce juglone 4 in 81 and 39% yields respectively.

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“…The preparation of the target compounds 3a-i was initiated with the synthesis of 2-acyl-1,4-dihydroxynaphthalenes 2a-c via solar photo-Friedel-Crafts acylation of 1,4naphthoquinone 1 with aldehydes according to a recently reported procedure [25]. Compounds 2a-c were then oxidized with silver (I) oxide in dichloromethane and the corresponding 2-acyl-1,4-naphthoquinones were in situ reacted with the selected phenylamines, in a one-pot procedure, to give the corresponding 3-acyl-2-phenylamino 1,4naphthoquinones 3a-i (Scheme 1).…”

Section: Chemistrymentioning

confidence: 99%

Biological Evaluation of 3-Acyl-2-Arylamino-1,4-Naphthoquinones as Inhibitors of Hsp90 Chaperoning Function

Ríos¹,

Benites²,

Valderrama³

et al. 2013

CTMC

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Hsp90 is a chaperone that plays a key function in cancer cells by stabilizing proteins responsible of cell growth and survival. Disruption of the Hsp90 chaperone machinery leads to the proteasomal degradation of its client proteins. Hsp90 appears then as an attractive target for the development of new anticancer molecules. We have shown that ascorbate-driven menadione-redox cycling inhibits Hsp90 activity by provoking an N-terminal cleavage of the protein, inducing the degradation of several of its client proteins. Since the mechanism involves an oxidative stress, we explored the effect of a series of diverse donor-acceptor 3-acyl-2-phenylamino 1,4-naphthoquinones on Hsp90 integrity, in the presence of ascorbate. Results show that quinone-derivatives that bear two electroactive groups (namely quinone and nitro) exhibit the highest inhibitory activity (Hsp90 cleavage and cell death). The biological activity of the series mainly relies on their redox capacity and their lipophilicity, which both modulate the ability of these compounds to induce a cytotoxic effect in K562 cells. As observed with other redox cycling quinones, the protein cleavage is blocked in the presence of N-terminal Hsp90 inhibitors suggesting that the availability or occupancy of nucleotide binding site in the N-terminal pocket of Hsp90 plays a critical role. In addition the survival of cancer cells and their metabolic and redox homeostasis were strongly impaired by the presence of ascorbate. Since these effects were similar to that obtained by ascorbate/menadione and they were blocked by the antioxidant N-acetylcyteine (NAC), it appears that oxidative stress is a major component of this cytotoxicity.

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The solar-chemical photo-Friedel–Crafts heteroacylation of 1,4-quinones

Cited by 37 publications

References 35 publications

Substituted 3-acyl-2-phenylamino-1,4-naphthoquinones intercalate into DNA and cause genotoxicity through the increased generation of reactive oxygen species culminating in cell death

Substituted 3-acyl-2-phenylamino-1,4-naphthoquinones intercalate into DNA and cause genotoxicity through the increased generation of reactive oxygen species culminating in cell death

Green Synthetic Approaches to Furoylnaphthohydroquinone and Juglone

Biological Evaluation of 3-Acyl-2-Arylamino-1,4-Naphthoquinones as Inhibitors of Hsp90 Chaperoning Function

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