- Hetero-annulation reaction between 2-acylnaphthoquinones and 2-aminobenzothiazoles. A new synthetic route to antiproliferative benzo[g]benzothiazolo[2,3-b]quinazoline-7,12-quinones
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A convenient two-step method is developed for the preparation of benzo[g]benzothiazolo[2,3-b]quinazoline-7,12-quinones from 2-acylnaphthohydroquinones and 2-aminobenzothiazoles. The structure of the heterocyclic quinones is supported by X-ray crystallography. This protocol provides an operationally simple strategy to prepare the title compounds and shows good functional flexibility and easily available starting materials. Evidences are reported on the significant in vitro antiproliferative activities of some of the obtained heterocyclic quinones on prostate, bladder, and breast human-derived tumor cell lines.
- Valderrama, Jaime A.,Ríos, David,Muccioli, Giulio G.,Buc Calderon, Pedro,Brito, Iván,Benites, Julio
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- An improved procedure for the photoacylation of 1,4-naphthoquinone with aliphatic aldehydes
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Irradiation of 1,4-naphthoquinone at 300±25 nm in benzene and in the presence of aliphatic aldehydes readily yields acylated hydroquinones in good to high yields. The developed protocol represents a significant improvement over the original procedure using medium-pressure mercury lamps. Subsequent oxidation gives the corresponding acylated quinones. Georg Thieme Verlag Stuttgart.
- Friedrichs, Ferdinand,Murphy, Brian,Nayrat, Delphine,Ahner, Torsten,Funke, Mario,Ryan, Michael,Lex, Johann,Mattay, Jochen,Oelgem?ller, Michael
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- In vitro inhibition of Hsp90 protein by benzothiazoloquinazolinequinones is enhanced in the presence of ascorbate. a preliminary in vivo antiproliferative study
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A series of benzo[g]benzothiazolo[2,3-b]quinazoline-7,12-quinones were prepared from 2-acylnaphthohydroquinones and 2-aminobenzothiazoles and were evaluated for their in vitro antiproliferative activity. After screening using the MTT reduction assay, their IC50 values were calculated on a panel of cancer cells (T24, DU-145, MCF-7). Current standard anticancer drugs were included as control, and their calculated IC50 values were 7.8 and 23.5 μM for 5-fluorouracil and tamoxifen, respectively. Non-cancer cells (AG1523) were included to assess cancer cell sensitivity and drug selectivity. Four members of the series, with IC50 values from 0.11 to 2.98 μM, were chosen for further assays. The selected quinones were evaluated regarding their effects on cancer cell proliferation (clonogenic assay) and on Hsp90 and poly(ADPribose)polymerase (PARP) protein integrity. The most active compound (i.e., 15) substantially inhibited colony forming unit (CFU) formation at 0.25 μM. In the presence of ascorbate, it induced an oxidative cleavage of Hsp90 but had no effect on PARP protein integrity. In an in vivo animal model, it discreetly increased the mean survival time (m.s.t.) of tumor-bearing mice. In light of these results, compound 15 represents a potential lead-molecule to be further developed.
- Benites, Julio,Calderon, Pedro Buc,Muccioli, Giulio G.,Ríos, David,Valderrama, Jaime A.
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- Synthetic approaches and: In vitro cytotoxic evaluation of 2-acyl-3-(3,4,5-trimethoxyanilino)-1,4-naphthoquinones
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2-Acyl-1,4-naphthoquinones react with 3,4,5-trimethoxyaniline, under aerobic conditions, to give benzophenanthridinequinone, benzocarbazole and 2-acyl-3-(3,4,5-trimethoxyanilino)-1,4-naphthoquinone derivatives. The formation of the heterocyclic compounds is discussed in terms of the ring closure of C-C Michael type adduct intermediates through two alternative N-C-bond formations. The propensity of the substrates to undergo preferential C-C instead of C-N bond formation and the further heterocyclization of the C-C Michael type adduct intermediates is rationalized by using product stability parameters assessed by DFT calculations. Preliminary results are reported on a convenient access towards 2-acyl-3-(3,4,5-trimethoxyanilino)-1,4-naphthoquinones from 2-acylnaphthoquinones and their cytotoxic activities on cancer cells.
- Valderrama, Jaime A.,Cabrera, Mónica,Benites, Julio,Ríos, David,Inostroza-Rivera, Ricardo,Muccioli, Giulio G.,Calderon, Pedro Buc
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p. 24813 - 24821
(2017/07/11)
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- Anti-tyrosinase, antioxidant, and antibacterial activities of novel 5-hydroxy-4-acetyl-2,3-dihydronaphtho[1,2- b ]furans
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Novel 5-hydroxy-4-acetyl-2,3-dihydronaphtho[1,2-b]furans (7a-k) were synthesized using ceric ammonium nitrate (CAN)-catalyzed formal [3 + 2] cycloaddition. Synthesized compounds were evaluated for their tyrosinase inhibitory, antioxidant, and antibacterial activities. A modified spectrophotometric method using l-DOPA as substrate was used to determine tyrosinase inhibitory activities, and a 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay was used to evaluate antioxidant properties. Antibacterial activities against gram-negative Escherichia coli (KCTC-1924) and gram-positive Staphylococcus aureus (KCTC-1916) were evaluated using the disc diffusion technique. Of the synthesized compounds, 7b with a 4-acetyl and an electron-enriched dihydronaphthofuran ring showed the highest tyrosinase-inhibition activity (IC50 Combining double low line 8.91 μg/mL), which was comparable with that of standard kojic acid (IC50 Combining double low line 10.16 μg/mL), potent antioxidant activity (IC50 Combining double low line 3.33 μg/mL), which was comparable with that of BHT (IC50 Combining double low line 34.67 μg/mL), and excellent antibacterial activities (MICs: 0.50 μg/mL against E. coli and S. aureus strains). A mechanistic analysis of 7b demonstrated that its tyrosinase inhibitory activity was reversible and competitive. Compounds 7c and 7d showed potent antioxidant activities (IC50: 6.30 and 5.01 μg/mL), and compound 7d also exhibited potent inhibitory activity against E. coli with a MIC of 0.5 μg/mL. Furthermore, compounds 7a, 7e, 7f, and 7i showed potent antibacterial activities against S. aureus with MICs of 0.5 μg/mL, which was comparable to that of ampicillin (MIC Combining double low line 0.5 μg/mL).
- Xia, Likai,Idhayadhulla, Akber,Lee, Yong Rok,Wee, Young-Jung,Kim, Sung Hong
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p. 605 - 612
(2015/01/16)
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- Synthesis of pyrrolo[3,2-b]benzofurans and pyrrolo[3,2-b]naphthofurans via addition of a silyloxypyrrole to activated quinones
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The uncatalyzed reaction of N-(tert-butoxycarbonyl)-2-tert- butyldimethylsilyloxypyrrole 3 with 1,4-quinones bearing an electron withdrawing group at C-2 has been studied. Use of 1,4-quinones 4, 5 bearing an ester group at C-2 provided an efficient synthe
- Brimble, Margaret A.,Burgess, Caryn,Halim, Rosliana,Petersson, Maria,Ray, Jayanta
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p. 5751 - 5758
(2007/10/03)
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- Oxidation of Hydroquinones and Hydroquinone Monomethyl Ethers to Quinones with tert-Butyl Hydroperoxide and Catalytic Amounts of Ceric Ammonium Nitrate (CAN)
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Mono- and bicyclic hydroquinones and hydroquinone monomethyl ethers 1, 2 are oxidized in 82-91% yield to the corresponding quinones using only 2 mol% of ceric ammonium nitrate (CAN) and 2.5 equivalents of tert-butyl hydroperoxide.
- Krohn, Karsten,Vitz, Juergen
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p. 825 - 827
(2007/10/03)
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- The Acetylation of Naphthoquinones. The Synthesis of 3-Acetyl-5-methoxy- and 3-Acetyl-5,7-dimethoxy-1,4-naphthoquinones
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The conversion of 5-methoxy- and 5,7-dimethoxy-1,4-naphthoquinones into their 3-acetyl derivatives is described.A key step is the Fries rearrangement of 1,5-dimethoxy-4-acetoxynaphthalenes to the corresponding 3-acetyl-4-naphthols with boron trifluoride-diethyl ether.Alternative Fries rearrangement of 1-acetoxy-4-hydroxy-5-methoxynaphthalenes gave the 3-acetylquinols, involving meta migration of the acetyl group.A convenient new synthesis of 2-acetyl-1,4-naphthoquinone is also reported.
- Chorn, Trevor A.,Giles, Robin G.F.,Green, Ivan R.,Hugo, Victor I.,Mitchell, Peter R.K.,Yorke, Selwyn C.
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p. 1339 - 1343
(2007/10/02)
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