- Ebenaceae extractives. Part 11. The synthesis of 7-methyljuglone. A re-examination
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The Friedel-Crafts reaction between maleic anhydride and 4-chloro-3-methylphenol yields, besides 8-chloro-5-hydroxy-7-methylnaphthoquinone 1, helminthosporin 5 and its 8-chloro derivative 6 and, after methylation, methyl (E)-β-(5-chloro-2-methoxy-4-methylbenzoyl)acrylate 4. Treatment of the chloronaphthoquinone 1 with tin(II) chloride in hydrochloric acid and tetrahydrofuran followed by iron(III) chloride converts it efficiently into 7-methyljuglone 2.
- Musgrave,Skoyles
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- Activity of 7-methyljuglone derivatives against Mycobacterium tuberculosis and as subversive substrates for mycothiol disulfide reductase
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The naphthoquinone 7-methyljuglone (5-hydroxy-7-methyl-1,4-naphthoquinone) has previously been isolated and identified as an active component of root extracts of Euclea natalensis which displays antitubercular activity. Herein, a series of synthetic and plant-derived naphthoquinone derivates of the 7-methyljuglone scaffold have been prepared and evaluated for antibacterial activity against Mycobacterium tuberculosis. Several of these compounds have been shown to operate as subversive substrates with mycothiol disulfide reductase. The absence of a direct correlation between antitubercular activity and subversive substrate efficiency with mycothiol disulfide reductase, might be a consequence of their non-specific reactivity with multiple biological targets (e.g. other disulfide reductases).
- Mahapatra, Anita,Mativandlela, Sannah P.N.,Binneman,Fourie,Hamilton, Chris J.,Meyer,van der Kooy,Houghton, Peter,Lall, Namrita
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- Cytotoxicity of synthesized 1,4-naphthoquinone analogues on selected human cancer cell lines
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In an effort to establish new candidates with enhanced anticancer activity of 5-hydroxy-7-methyl-1,4-naphthoquinone scaffold (7-methyljuglone) previously isolated from the root extract of Euclea natalensis, a series of 7-methyljuglone derivatives have been synthesized and assessed for cytotoxicity on selected human cancer lines. These compounds were screened in vitro for anticancer activity on MCF-7, HeLa, SNO and DU145 human cancer cell lines by MTT assay. Most of them exhibited significant toxicity on cancer cell lines with lower IC50 values. The most potent derivative (19) exhibited the toxicity on HeLa and DU145 cell lines with IC50 value of 5.3 and 6.8 μM followed by compound (5) with IC50 value of 10.1 and 9.3 μM, respectively. Structure-activity relationship reveals that the fluoro substituents at position C-8 while hydroxyl substituents at C-2 and C-5 positions played an important role in toxicity.
- Kishore, Navneet,Binneman, Brigitte,Mahapatra, Anita,Van De Venter, Maryna,Du Plessis-Stoman, Debbie,Boukes, Gerhardt,Houghton, Peter,Marion Meyer,Lall, Namrita
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- Synthesis and HIV-1 reverse transcriptase inhibition activity of 1,4-naphthoquinone derivatives
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Some 1,4-napthoquinone derivatives were synthesized, and dimers of 5-hydroxy-7-methyl-1,4-naphthoquinone (5) were isolated from the roots of Euclea natalensis. Their structures were confirmed by spectroscopic (UV, IR, NMR, and MS) analysis. The HIV-1 reverse transcriptase inhibition activity of the compounds against recombinant HIV-1 enzyme was studied in vitro (non-radioactive HIV-RT colorimetric assay) using the Roche Diagnostic kit and compared with that of doxorubicin as standard drug. Some of the synthesized compounds exhibited exceptionally potent (91-100%) HIV-1 RT inhibition at 100 μg/mL concentration. Surprisingly the dimers showed very weak activity.
- Mahapatra, Anita,Tshikalange,Meyer,Lall, Namrita
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- New naphthoquinone derivatives against glioma cells
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This work was aimed to the development of a set of new naphtoquinone derivatives that can act against glioma. The compounds were tested in order to find out their ability to inhibit the growth of glioma cells, and the results of these assays were correlated with electrochemical analysis and NMR-based reoxidation kinetic studies, suggesting that a redox mechanism underlies and may explain the observed biological behavior. In addition to a full description of the synthetic pathways, electrochemistry, NMR and single crystal X-ray diffraction data are provided.
- Redaelli, Marco,Mucignat-Caretta, Carla,Isse, Abdirisak Ahmed,Gennaro, Armando,Pezzani, Raffaele,Pasquale, Riccardo,Pavan, Valeria,Crisma, Marco,Ribaudo, Giovanni,Zagotto, Giuseppe
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p. 458 - 466
(2015/05/05)
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- Chemoenzymatic synthesis of novel C-ribosylated naphthoquinones
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The biological activity of many natural products is dependent on the presence of carbohydrate units, which are usually attached via an O-glycosidic linkage by glycosyltransferases. Recently, an exceptional C-ribosylation event was discovered in the biosynthesis of the polyketide antibiotic alnumycin A. The two-step process involves initial attachment of d-ribose-5-phosphate to the polyaromatic aglycone by the C-glycosynthase AlnA and subsequent dephosphorylation by AlnB, an enzyme of the haloacid dehalogenase family. Here, we tested 23 unnatural substrates to probe the C-ribosylation reaction. The chemoenzymatic synthesis of C-ribosylated juglone, 7-methyl juglone, monomethyl naphthazarin, 8-chloro-7-methyl juglone, and 9-hydroxy-1,4-anthraquinone revealed the importance of a 1,4-quinoid system with an adjacent phenolic ring in order for reaction to occur. To further rationalize the molecular basis for reactivity, factors governing substrate recognition were investigated by NMR binding experiments. Additionally, the suitability of substrates for nucleophilic substitution was assessed by molecular modeling using density functional theory (DFT) calculations.
- Blauenburg, Bastian,Oja, Terhi,Klika, Karel D.,Metsae-Ketelae, Mikko
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p. 2377 - 2382
(2013/12/04)
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- Dimeric Naphthoquinones, 17. Synthesis of Stypandrone and Dianellinone
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The naphthoquinone stypandrone (2b) ist synthesized via the intermediates 5a, 6a and 6b.Selective monoalkylation of its hydroquinone yields the monoether 12b, which, on phenol oxidation and oxidative dealkylation, leads to 13 and dianellinone (2a).The synthesis confirms the 3,3'-dimerisation of the natural product. - Keywords: Naphthoquinones, Stypandrone, Dianellinone, Phenol Oxidation
- Laatsch, Hartmut
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p. 377 - 385
(2007/10/02)
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- Dimeric Naphthoquinones, IV1). - Synthesis of Biramentaceone, Mamegakinone and Rotundiquinone
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Mamegakinone (8a), biramentaceone (12a), 3,3'-bijuglone (8b), 2,2-bijuglone (12b) and their methyl ethers were prepared by oxidative coupling of substituted 4-methoxy-1-naphthols; indigoids like 24 are intermediates.Cooxidation of the isomeric dimethoxy-1
- Laatsch, Hartmut
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p. 1321 - 1347
(2007/10/02)
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