4707-32-8Relevant academic research and scientific papers
Redox Center Modification of Lapachones towards the Synthesis of Nitrogen Heterocycles as Selective Fluorescent Mitochondrial Imaging Probes
dos Santos, Fabíola S.,Dias, Gleiston G.,de Freitas, Rossimiriam P.,Santos, Lucas S.,de Lima, Guilherme F.,Duarte, Hélio A.,de Simone, Carlos A.,Rezende, Lidia M. S. L.,Vianna, Monique J. X.,Correa, José R.,Neto, Brenno A. D.,da Silva Júnior, Eufranio N.
, p. 3763 - 3773 (2017)
We describe herein a synthetic strategy for the synthesis of new fluorescent imidazole and phenazine derivatives synthesized from lapachol, a naturally occurring naphthoquinone isolated from Tabebuia species (ipê tree). The photophysical properties and computational details of these compounds have been studied, aiming at gaining a complete understanding of the potential of these derivatives as probes capable of staining mitochondria selectively. Cell imaging experiments proved the capacity of the imidazole derivatives as selective fluorescent mitochondrial imaging probes. These heterocycles present the same staining patterns as MitoTracker Red, corroborating the potential of these compounds as new mitochondria markers permeable to the cell membrane.
Cytotoxic germacrane-type sesquiterpenes, pimarane-type diterpenes, and a naphthalene derivative from Wollastonia biflora
Chen, Wenliang,Tang, Weidong,Zhang, Rujun,Lou, Liguang,Zhao, Weimin
, p. 567 - 570 (2007)
Phytochemical investigation of the whole plants of Wollastonia biflora led to the isolation and identification of three new germacrane-type sesquiterpenes (1-3), two new pimarane-type diterpenes (4, 5), and a new naphthalene glycoside (6), along with 11 known compounds. Their structures were characterized on the basis of spectroscopic analyses and chemical methods. Compounds 1, 2, and 3 showed significant cytotoxic activity against me growth of hepatocellular carcinoma BEL-7402 cells in vitro.
Antiproliferative activity of synthetic naphthoquinones related to lapachol. First synthesis of 5-hydroxylapachol
Bonifazi, Evelyn L.,Ríos-Luci, Carla,León, Leticia G.,Burton, Gerardo,Padrón, José M.,Misico, Rosana I.
, p. 2621 - 2630 (2010)
A series of 5-hydroxy-1,4-naphthoquinones analogues was synthesized from juglone (6) and their antiproliferative activity against a representative panel of six human solid tumor cell lines has been investigated. The 2,5-dihydroxy-3-(3-methylbut-2-enyl)naphthalene-1,4-dione (4) and 2,3-dihydro-5-hydroxy-2-(prop-1-en-2-yl)naphtho[2,3-b]furan-4,9-dione (27) were the most potent antiproliferative agents with GI50 values of 0.42-8.1 and 0.80-2.2 μM, respectively. The results provide insight into the correlation between some structural properties of 5-hydroxynaphthoquinones and their antiproliferative activity.
Studies on the trypanocidal activity of semi-synthetic pyran[b-4,3] naphtho[1,2-d]imidazoles from β-lapachone
De Moura, Kelly C.G.,Salomao, Kelly,Menna-Barreto, Rubem F.S.,Emery, Flavio S.,Pinto, Maria Do Carmo F.R.,Pinto, Antonio V.,De Castro, Solange L.
, p. 639 - 645 (2004)
We synthesized new naphthoimidazoles from β-lapachone with an aromatic moiety linked to the imidazole ring, using phenylic and heterocyclic aldehydes. The most active compound against Trypanosoma cruzi had a p-methyl group linked to the phenyl ring, presenting an EC50 value of 15.5 ± 2.9 μM. No reliable correlation could be established with the biological activity and the structure of in the phenylic series. For the heterocyclic series, activity was associated with a three bond-distance from nitrogen to the imidazole ring, in accordance with our previous work.
Electronic structure and gas-phase chemistry of protonated α- And β-quinonoid compounds: A mass spectrometry and computational study
Vessecchi, Ricardo,Emery, Flávio S.,Lopes, Norberto P.,Galembeck, Sérgio E.
, p. 816 - 824 (2013)
Rationale: The use of quinonoid compounds against tropical diseases and as antitumor agents has prompted the search for new naturally occurring and synthetic derivatives. Among these quinonoid compounds, lapachol and its isomers (α- and β-lapachone) serve as models for the synthesis of new compounds with biological activity, and the use of electrospray ionization tandem mass spectrometry (ESI-MS/MS) analysis as a tool to elucidate and characterize these products has furnished important information about these compounds. Methods: ESI-MS/MS analysis under collision-induced dissociation conditions was used to describe the fragmentation mechanisms for protonated 1,4-naphthoquinone, 1,2-naphthoquinone, α-lapachone, and β-lapachone. The B3LYP/6-31+G(d,p) model was used to obtain proton affinities, gas-phase basicities, and molecular electrostatic potential maps, thus indicating the probable protonation sites. Fragmentation pathways were suggested on the basis of the relative enthalpies of the product ions. Results: The ESI-MS signals of the cationized molecules of ortho quinonoid compounds were more intense than those of the protonated molecule. Formation of the major product ions with m/z 187 from protonated α- and β-lapachone has been attributed to a retro-Diels-Alder (RDA) reaction. Conclusions: MS/MS studies on lapachol isomers (α- and β-lapachone) will facilitate the interpretation of the liquid chromatography (LC)-MS/MS analysis of new metabolites. MS/MS data on the 1,4-naphthoquinone, 1,2-naphthoquinone, α-lapachone and β-lapachone core will help characterize new derivatives from in vitro/in vivo metabolism studies in complex matrices. The product ions revealed the major fragmentation mechanisms and these ions will serve as diagnostic ions to identify each studied compound. Copyright
Lysosome-oriented, dual-stage pH-responsive polymeric micelles for β-lapachone delivery
Zhou, Yinjian,Dong, Ying,Huang, Gang,Wang, Yiguang,Huang, Xiaonan,Zhang, Fayun,Boothman, David A.,Gao, Jinming,Liang, Wei
, p. 7429 - 7440 (2016)
β-Lapachone (β-lap), a novel anticancer agent, is bioactivated by NADP(H):quinone oxidoreductase 1 (NQO1), an enzyme over-expressed in numerous tumors, including lung, pancreas, breast, and prostate cancers. Fast renal clearance and methemoglobinemia/hemolytic side-effects from the clinical formulation (β-lap-hydroxyl propyl-β-cyclodextrin complex) hindered its clinical translation. Here, we investigated dual-model pH-responsive polymers for β-lap delivery. Three pH-sensitive linkages, including acylhydrazone, ketal and imine bonds for β-lap prodrug syntheses result in an aryl imine linkage as the most optimal linkage. The conversion to β-lap was 2.8%, 4.5% and 100% at pH 7.4, 6.5 and 5.0 in 8 h, respectively. The β-lap aryl imine prodrug conjugated ultra-pH-sensitive (UPS) polymer reached high β-lap loading density (8.3%) and exhibited dual-stage responsiveness to pH variation. In pHs under pHt, at stage I, micelles immediately dissociate and subsequently, entering stage II, micelles start to quickly release β-lap. An in vitro release study showed that the micelles constantly release β-lap (14.9 ± 0.1%) at pHs above pHt in 72 h, whereas there was a boosted release of β-lap (79.4 ± 1.2%) at pH 5.0. The micelles' intracellular distribution being predominantly in the lysosome organelle guaranteed their pH-responsive dissociation and subsequently β-lap controlled release. The M-P micelles retained NQO1-dependent cytotoxicity in A549 lung cancer cells, similar to the free drug in both efficacy and mechanism of cell death. The lysosome-oriented dual-stage ultra-pH-responsive β-lap prodrug micelles potentially offer an alternative nanotherapeutic strategy for lung cancer, as well as other NQO1+ cancer therapies.
Selective endocytic trafficking in live cells with fluorescent naphthoxazoles and their boron complexes
Dias, Gleiston G.,Rodrigues, Bernardo L.,Resende, Jarbas M.,Calado, Hállen D. R.,De Simone, Carlos A.,Silva, Valter H. C.,Neto, Brenno A. D.,Goulart, Marilia O. F.,Ferreira, Fabricia R.,Meira, Assuero S.,Pessoa, Claudia,Correa, José R.,Da Silva Júnior, Eufranio N.
, p. 9141 - 9144 (2015)
Fluorescent naphthoxazoles and their boron derivatives have been synthesized and applied as superior and selective probes for endocytic pathway tracking in live cancer cells. The best fluorophores were compared with the commercially available acridine orange (co-staining experiments), showing far better selectivity.
Novel fluorescent lapachone-based BODIPY: Synthesis, computational and electrochemical aspects, and subcellular localisation of a potent antitumour hybrid quinone
Gontijo, Talita B.,De Freitas, Rossimiriam P.,De Lima, Guilherme F.,De Rezende, Lucas C. D.,Pedrosa, Leandro F.,Silva, Thaissa L.,Goulart, Marilia O.F.,Cavalcanti, Bruno C.,Pessoa, Claudia,Bruno, Marina P.,Corrêa, José R.,Emery, Flavio S.,Da Silva Júnior, Eufranio N.
, p. 13281 - 13284 (2016)
For the first time, a fluorescent lapachone-based BODIPY was synthesised and characterised by NMR and mass spectrometry. Computational and electrochemical aspects, as well as cytotoxic activity and subcellular localisation, were studied. Confocal microscopy experiments indicated that the probe was a specific mitochondria-staining agent. These in-detail analyses were useful in understanding the cytotoxic effects and mechanism of action of this novel hybrid compound. This molecule constitutes a promising prototype owing to its potential biological activities and the new strategies aimed at mechanistic investigations in cells and in vivo, and opens up an interesting avenue of research.
Synthesis of pharmacologically important naphthoquinones and anticancer activity of 2-benzyllawsone through DNA topoisomerase-II inhibition
Kumar, Balagani Sathish,Ravi, Kusumoori,Verma, Amit Kumar,Fatima, Kaneez,Hasanain, Mohammad,Singh, Arjun,Sarkar, Jayanta,Luqman, Suaib,Chanda, Debabrata,Negi, Arvind S.
, p. 1364 - 1373 (2017)
Naphthoquinones are naturally occurring biologically active entities. Practical de novo syntheses of three naphthoquinones i.e. lawsone (1), lapachol (2), and β-lapachone (3b) have been achieved from commercially available starting materials. The conversion of lapachol (2) to β-lapachone (3b) was achieved through p-TSA/Iodine/BF3-etherate mediated regioselective cyclisation. Further, 2-alkyl and 2-benzyllawsone derivatives have been prepared as possible anticancer agents. Four derivatives exhibited significant anticancer activity and the best analogue i.e. compound 21a exhibited potential anticancer activity (IC50?=?5.2?μM) against FaDu cell line. Compound 21a induced apoptosis through activation of caspase pathway and exerted cell cycle arrest at S phase in FaDU cells. It also exhibited significant topoisomerase-II inhibition activity. Compound 21a was found to be safe in Swiss albino mice up to 1000?mg/kg oral dose.
α- and β-Lapachone Isomerization in Acidic Media: Insights from Experimental and Implicit/Explicit Solvation Approaches
Delarmelina, Maicon,Nicoletti, Caroline D.,de Moraes, Marcela C.,Futuro, Debora O.,Bühl, Michael,de C. da Silva, Fernando,Ferreira, Vitor F.,de M. Carneiro, José W.
, p. 52 - 61 (2019)
Combined experimental and mixed implicit/explicit solvation approaches were employed to gain insights into the origin of switchable regioselectivity of acid-catalyzed lapachol cyclization and α-/β-lapachone isomerization. It was found that solvating species under distinct experimental conditions stabilized α- and β-lapachone differently, thus altering the identity of the thermodynamic product. The energy profile for lapachol cyclization revealed that this process can occur with low free-energy barriers (lower than 8.0 kcal mol?1). For α/β isomerization in a dilute medium, the computed enthalpic barriers are 15.1 kcal mol?1 (α→β) and 14.2 kcal mol?1 (β→α). These barriers are lowered in concentrated medium to 11.5 and 12.6 kcal mol?1, respectively. Experimental determination of isomers ratio was quantified by HPLC and NMR measurements. These findings provide insights into the chemical behavior of lapachol and lapachone derivatives in more complex environments.
