- Molluscicidal activity of synthetic lapachol amino and hydrogenated derivatives
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A series of new amino derivatives and a new partially hydrogenated derivative of the natural naphthoquinone lapachol were found to exhibit molluscicidal activity against Biomphalaria glabrata. A series of new amino derivatives and a new partially hydrogenated derivative of the natural naphthoquinone lapachol were assayed for molluscicidal activity against Biomphalaria glabrata. These derivatives showed low to medium LC50 values, and a 3.1 μg/mL value for the most potent derivative of the series. The toxicity is in agreement with the decrease of polar character of the tested compounds.
- Silva, Tania M.S.,Camara, Celso A.,Barbosa, Ticiano P.,Soares, André Z.,Da Cunha, Luciana C.,Pinto, Angelo C.,Vargas, Maria D.
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- Synthesis and pharmacological activity of diterpenylnaphthoquinone derivatives
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New diterpenylquinones, combining a diterpene diacid and a naphthoquinone, were prepared from junicedric acid and lapachol. The new derivatives were assessed as gastroprotective agents by the HCl-EtOH-induced gastric lesions model in mice as well as for basal cytotoxicity on the following human cell lines: Normal lung fibroblasts (MRC-5), gastric epithelial adenocarcinoma (AGS), and hepatocellular carcinoma (Hep G2). Several of the new compounds were significantly active as antiulcer agents and showed selective cytotoxicity against AGS cells.
- Pertino, Mariano Walter,Theoduloz, Cristina,Palenzuela, Jose Antonio,Del Mar Afonso, Maria,Yesilada, Erdem,Monsalve, Francisco,Gonzalez, Paulo,Droguett, Daniel,Schmeda-Hirschmann, Guillermo
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- Total Synthesis of Hybocarpone and Analogues Thereof. A Facile Dimerization of Naphthazarins to Pentacyclic Systems
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The total synthesis of the lichen-derived antitumor agent hybocarpone (1) and related compounds is described. The successful route to hybocarpone features a novel radical-based dimerization/hydration cascade which generates the bridging hindered carbon-ca
- Nicolaou,Gray, David L. F.
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- Gas-phase reactivity of 2-hydroxy-1,4-naphthoquinones: A computational and mass spectrometry study of lapachol congeners
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In order to understand the influence of alkyl side chains on the gas-phase reactivity of 1,4-naphthoquinone derivatives, some 2-hydroxy-1,4-naphthoquinone derivatives have been prepared and studied by electrospray ionization tandem mass spectrometry in combination with computational quantum chemistry calculations. Protonation and deprotonation sites were suggested on the basis of gas-phase basicity, proton affinity, gas-phase acidity (?G acid), atomic charges and frontier orbital analyses. The nature of the intramolecular interaction as well as of the hydrogen bond in the systems was investigated by the atoms-in-molecules theory and the natural bond orbital analysis. The results were compared with data published for lapachol (2-hydroxy-3-(3-methyl-2-butenyl)-1,4-naphthoquinone). For the protonated molecules, water elimination was verified to occur at lower proportion when compared with side chain elimination, as evidenced in earlier studies on lapachol. The side chain at position C(3) was found to play important roles in the fragmentation mechanisms of these compounds.
- Vessecchi, Ricardo,Emery, Flávio S.,Galembeck, Sérgio E.,Lopes, Norberto P.
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- Diterpenylquinone hybrids: Synthesis and assessment of gastroprotective mechanisms of action in human cells
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A modern approach in the search for new bioactive molecules is the synthesis of novel chemical entities combining molecules of different biosynthetic origin presenting biological effects as single compounds. Gastroprotective compounds from South American medicinal plants, namely quinones and diterpenes, were used as building blocks to obtain hybrid diterpenylquinones. Starting from the labdane diterpene junicedric acid and two isomers, as well as from three quinones, including lapachol, 18 hybrid molecules were synthesized. Six of them are described for the first time. The potential gastroprotective mechanisms of action of the compounds were assessed in dose-response experiments using human gastric epithelial cells (AGS) and human lung fibroblasts (MRC-5). The following studies were carried out: stimulation of cell proliferation, cytoprotection against sodium taurocholate (NaT)-induced damage, synthesis of PGE2 and total reduced sulfhydryl (GSH) content. The antioxidant capacity of the compounds was determined on the inhibition of the lipoperoxidation in human erythrocyte membranes. Hybrid compounds presented activities different from those shown by the starting compounds, supporting the potential of this approach in the search for new bioactive molecules. The effects might be modulated by selective modification in the terpene or quinone moieties of the new molecules. Structure-activity relationships are discussed.
- Theoduloz, Cristina,Bravo, Ivanna,Pertino, Mariano Walter,Schmeda-Hirschmann, Guillermo
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- Ligand-based design, synthesis and biochemical evaluation of potent and selective inhibitors of Schistosoma mansoni dihydroorotate dehydrogenase
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Schistosomiasis ranks second only to malaria as the most common parasitic disease worldwide. 700 million people are at risk and 240 million are already infected. Praziquantel is the anthelmintic of choice but decreasing efficacy has already been documented. In this work, we exploited the inhibition of Schistosoma mansoni dihydroorotate dehydrogenase (SmDHODH) as a strategy to develop new therapeutics to fight schistosomiasis. A series of quinones (atovaquone derivatives and precursors) was evaluated regarding potency and selectivity against both SmDHODH and human DHODH. The best compound identified is 17 (2-hydroxy-3-isopentylnaphthalene-1,4-dione) with IC50 = 23 ± 4 nM and selectivity index of 30.83. Some of the new compounds are useful pharmacological tools and represent new lead structures for further optimization.
- Calil, Felipe A.,David, Juliana S.,Chiappetta, Estela R.C.,Fumagalli, Fernando,Mello, Rodrigo B.,Leite, Franco H.A.,Castilho, Marcelo S.,Emery, Flavio S.,Nonato, M.Cristina
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p. 357 - 366
(2019/02/19)
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- Organocatalytic Asymmetric Formal [3+2] Cycloaddition as a Versatile Platform to Access Methanobenzo[7]annulenes
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Pharmaceutically and structurally important methanobenzo[7]annulenes were synthesized in very good yields with excellent enantio- and diastereoselectivities through an unprecedented organocatalytic formal [3+2] cycloaddition from readily available 2-alkyl-3-hydroxynaphthalene-1,4-diones and alkyl vinyl ketones.
- Ramachary, Dhevalapally B.,Anif Pasha, Mohammed,Thirupathi, Guguloth
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supporting information
p. 12930 - 12934
(2017/09/13)
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- Synthesis and evaluation of quinonoid compounds against tumor cell lines
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Thirty two compounds were synthesized in moderate to high yields and showed activity against cancer cells HL-60 (leukemia), MDA-MB435 (melanoma), HCT-8 (colon) and SF295 (central nervous system), with IC50 below 2 μM for some compounds. The β-lapachone-based 1,2,3-triazoles showed the best cytoxicity profile and emerge as promising anticancer prototypes. Insights about the reactive oxygen species (ROS) mechanism of anticancer action for some compounds were obtained by addition of 1-bromoheptane that deplete reduced glutathione (GSH) content and by using N-acetylcysteine that protects cells against apoptotic cellular death, as well by analysis of thiobarbituric acid reactive substances (TBARS) formation, and oxidative DNA damage after treatment detected by the comet assay with the bacterial enzymes formamidopyrimidine DNA-glycosylase (FPG) and endonuclease III (ENDOIII).
- Da Silva Jr., Eufranio N.,Cavalcanti, Bruno C.,Guimar?es, Tiago T.,Pinto, Maria Do Carmo F.R.,Cabral, Igor O.,Pessoa, Cláudia,Costa-Lotufo, Letícia V.,De Moraes, Manoel O.,De Andrade, Carlos K.Z.,Dos Santos, Marcelo R.,De Simone, Carlos A.,Goulart, Marilia O.F.,Pinto, Antonio V.
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scheme or table
p. 399 - 410
(2011/02/27)
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- Quinonoid and phenazine compounds: Synthesis and evaluation against H 37Rv, rifampicin and isoniazid-resistance strains of Mycobacterium tuberculosis
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Several quinonoid and phenazine compounds were synthesized in moderate to high yields and showed activity against H37Rv, rifampicin and isoniazid-resistance strains of Mycobacterium tuberculosis. The cytotoxity of the compounds were evaluated against human peripheral blood mononuclear cells (PBMC) and these substances emerge as promising antitubercular prototypes.
- Carneiro, Paula F.,Pinto, Maria Do Carmo F.R.,Coelho, Tatiane S.,Cavalcanti, Bruno C.,Pessoa, Cláudia,De Simone, Carlos A.,Nunes, Isabelle K.C.,De Oliveira, Nathalia M.,De Almeida, Renata G.,Pinto, Antonio V.,De Moura, Kelly C.G.,Da Silva, Pedro A.,Da Silva Júnior, Eufranio N.
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scheme or table
p. 4521 - 4529
(2011/11/06)
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- Synthesis and pharmacophore modeling of naphthoquinone derivatives with cytotoxic activity in human promyelocytic leukemia HL-60 cell line
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Catalyst/HypoGen pharmacophore modeling approach and three-dimensional quantitative structure-activity relationship (3D-QSAR)/comparative molecular similarity indices analysis (CoMSIA) methods have been successfully applied to explain the cytotoxic activity of a set of 51 natural and synthesized naphthoquinone derivatives tested in human promyelocytic leukemia HL-60 cell line. The computational models have facilitated the identification of structural elements of the ligands that are key for antitumoral properties. The four most salient features of the highly active β-cycled-pyran-1,2-naphthoquinones [0.1 μM 50 0.6 μM] are the hydrogen-bond interactions of the carbonyl groups at C-1 (HBA1) and C-2 (HBA2), the hydrogen-bond interaction of the oxygen atom of the pyran ring (HBA3), and the interaction of methyl groups (HYD) at the pyran ring with a hydrophobic area at the receptor. The moderately active 1,4-naphthoquinone derivatives accurately fulfill only three of these features. The results of our study provide a valuable tool in designing new and more potent cytotoxic analogues.
- Pérez-Sacau, Elisa,Díaz-Peńate, Raquel G.,Estévez-Braun, Ana,Ravelo, Angel G.,García-Castellano, Jose M.,Pardo, Leonardo,Campillo, Mercedes
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p. 696 - 706
(2008/02/01)
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- Reaction of 2-Hydroxy-1,4-naphthoquinone with Aldehydes. Synthesis of 2-Hydroxy-3-alk-1-enylnaphthoquinones.
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In the course of an unsuccessful attempt to prepare 2-(3,7-dimethylocta-1,6-dienyl)-3-hydroxy-1,4-naphthoquinone (1a) by acid catalyzed condensation of 2-hydroxy-1,4-naphthoquinone (2) with citronellal, a tetracyclic quinone (3) was obtained.This quinone
- Bock, Klaus,Jacobsen, Niels,Terem, Bulent
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p. 659 - 664
(2007/10/02)
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