RESUMO
A series of 2-phenylamino-3-acyl-1,4-naphtoquinones were evaluated regarding their in vitro antiproliferative activities using DU-145, MCF-7 and T24 cancer cells. Such activities were discussed in terms of molecular descriptors such as half-wave potentials, hydrophobicity and molar refractivity. Compounds 4 and 11 displayed the highest antiproliferative activity against the three cancer cells and were therefore further investigated. The in silico prediction of drug likeness, using pkCSM and SwissADME explorer online, shows that compound 11 is a suitable lead molecule to be developed. Moreover, the expressions of key genes were studied in DU-145 cancer cells. They include genes involved in apoptosis (Bcl-2), tumor metabolism regulation (mTOR), redox homeostasis (GSR), cell cycle regulation (CDC25A), cell cycle progression (TP53), epigenetic (HDAC4), cell-cell communication (CCN2) and inflammatory pathways (TNF). Compound 11 displays an interesting profile because among these genes, mTOR was significantly less expressed as compared to control conditions. Molecular docking shows that compound 11 has good affinity with mTOR, unraveling a potential inhibitory effect on this protein. Due to the key role of mTOR on tumor metabolism, we suggest that impaired DU-145 cells proliferation by compound 11 is caused by a reduced mTOR expression (less mTOR protein) and inhibitory activity on mTOR protein.
Assuntos
Antineoplásicos , Naftoquinonas , Neoplasias , Naftoquinonas/farmacologia , Simulação de Acoplamento Molecular , Linhagem Celular Tumoral , Proliferação de Células , Apoptose , Serina-Treonina Quinases TOR/metabolismo , Antineoplásicos/farmacologia , Ensaios de Seleção de Medicamentos AntitumoraisRESUMO
The reaction of 2-acyl-1,4-naphthoquinones with N,N-dimethylaniline and 2,5-dimethoxyaniline, promoted by catalytic amounts of CeCl3·7H2O under "open-flask" conditions, produced a variety of 2-acyl-3-aminophenyl-1,4-naphthoquinones structurally related to the cytotoxic 2-acetyl-3-phenyl-1,4-naphthoquinone, an inhibitor of the heat shock chaperone protein Hsp90. The members of the 2-acyl-3-aminophenyl-1,4-naphthoquinone series were isolated in good yields (63-98%). The cyclic voltammograms of the 2-acyl-3-aminophenyl-1,4-naphthoquinone exhibit two one-electron reduction waves to the corresponding radical-anion and dianion and two quasireversible oxidation peaks. The first and second half-wave potential values (E 1/2) of the members of the series are sensitive to the push-pull electronic effects of the substituents in the naphthoquinone scaffold. Furthermore, the in vitro antiproliferative properties of these new quinones were evaluated on two human cancer cells DU-145 (prostate) and MCF-7 (mammary) and a nontumorigenic HEK-293 (kidney) cell line, using the MTT colorimetric method. Two members, within the series, exhibited interesting cytotoxic activities on human prostate and mammary cancer cells.
Assuntos
Antineoplásicos/farmacologia , Proliferação de Células/efeitos dos fármacos , Naftoquinonas/farmacologia , Antineoplásicos/síntese química , Antioxidantes/análise , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais , Técnicas Eletroquímicas , Feminino , Células HEK293 , Humanos , Masculino , Naftoquinonas/química , Oxirredução , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Relação Estrutura-AtividadeRESUMO
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.
Assuntos
Antineoplásicos , Proliferação de Células/efeitos dos fármacos , Proteínas de Choque Térmico HSP90 , Proteínas de Neoplasias , Neoplasias Experimentais , Quinazolinas , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Antineoplásicos/farmacologia , Ácido Ascórbico , Proteínas de Choque Térmico HSP90/antagonistas & inibidores , Proteínas de Choque Térmico HSP90/metabolismo , Humanos , Células MCF-7 , Camundongos , Proteínas de Neoplasias/antagonistas & inibidores , Proteínas de Neoplasias/metabolismo , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/metabolismo , Neoplasias Experimentais/patologia , Quinazolinas/síntese química , Quinazolinas/química , Quinazolinas/farmacologia , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
A broad range of 3-acyl-2,5-bis(phenylamino)-1,4-benzoquinones were synthesized and their voltammetric values, as well as in vitro cancer cell cytotoxicities, were assessed. The members of this series were prepared from acylbenzoquinones and phenylamines, in moderate to good yields (47-74%), through a procedure involving a sequence of two in situ regioselective oxidative amination reactions. The cyclic voltammograms of the aminoquinones exhibit two one-electron reduction waves to the corresponding radical-anion and dianion, and two quasi-reversible oxidation peaks. The first and second half-wave potential values (E1/2) of the members of the series were sensitive to the push-pull electronic effects of the substituents around the benzoquinone nucleus. The in vitro cytotoxic activities of the 3-acyl-2,5-bis(phenylamino)-1,4-benzoquinones against human cancer cells (bladder and prostate) and non-tumor human embryonic kidney cells were measured using the MTT colorimetric method. The substitution of both aniline groups, by either methoxy (electron donating effect) or fluorine (electron withdrawal effect), decreased the cytotoxicity in the aminoquinones. Among the members of the unsubstituted phenylamino series, two of the 18 compounds showed interesting anti-cancer activities. A preliminary assay, looking for changes in the expression of selected genes, was performed. In this context, the two compounds increased TNF gene expression, suggesting an association with an inflammatory-like response.
Assuntos
Benzoquinonas/farmacologia , Neoplasias/patologia , Antineoplásicos/química , Antineoplásicos/farmacologia , Benzoquinonas/química , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Células HEK293 , Humanos , Concentração Inibidora 50 , Conformação Molecular , Neoplasias/genéticaRESUMO
The composition of the essential oil obtained by hydrodistillation from Minthostachys mollis Griseb (Lamiaceae) aerial parts was determined by GC and GC/MS. Menthone (13.2%), pulegone (12.4%), cis-dihydrocarvone (9.8%) and carvacrol acetate (8.8%) were the main essential oil components. The cytotoxic activity of the essential oil was in vitro measured using the MTT colorimetric assay. IC50 values were calculated on healthy non-tumor cells (HEK-293) and three human cancer cell lines (T24, DU-145 and MCF-7). In such latter cells, the estimated values were around 0.2 mg/mL. In addition, the antioxidant activity was determined by interaction with the stable free radical 2,2"-diphenyl-1-picrylhydrazyl. The essential oil was almost devoid of antioxidant activity indicating that its anti-proliferative action relies on other unknown mechanism.
La composicioÌn del aceite esencial obtenido por hidrodestilacioÌn a partir de partes aeÌreas de Minthostachys mollis Griseb (Lamiaceae) se determinoÌ mediante GC y GC/MS. Mentona (13.2%), pulegona (12.4%), junto con cis-dihidrocarvona (9.8%) y acetato de carvacrol (8.8%) fueron los principales componentes del aceite esencial. La actividad citotoÌxica del aceite esencial se midioÌ in vitro utilizando el ensayo colorimeÌtrico MTT tanto en ceÌlulas sanas no tumorales (HEK-293) como en tres liÌneas celulares de caÌncer humano (T24, DU-145 y MCF-7). Los valores de IC50 calculados fueron de alrededor de 0.2 mg/mL. AdemaÌs, se determinoÌ la actividad antioxidante por su interaccioÌn con el radical libre 2,2"-difenil-1-picrilhidrazilo. El aceite esencial tiene baja actividad antioxidante, lo que indica que su accioÌn antiproliferativa depende de otro mecanismo desconocido.
Assuntos
Óleos Voláteis/farmacologia , Lamiaceae , Linhagem Celular Tumoral/efeitos dos fármacos , Antioxidantes/farmacologia , Peru , Picratos , Terpenos/análise , Bioensaio , Compostos de Bifenilo , Calorimetria , Óleos Voláteis/química , Sobrevivência Celular/efeitos dos fármacos , Sequestradores de Radicais Livres , Cromatografia Gasosa-Espectrometria de Massas , Antioxidantes/químicaRESUMO
The composition of the essential oil obtained by hydrodistillation from Dalea strobilacea Barneby (Fabaceae) aerial parts was examined by GC and GC/MS. beta-Phellandrene (44 percent) together with alpha-pinene (18 percent) were the main essential oil components. Antimicrobial activity of the essential oil was evaluated against eight bacterial strains. A moderate growth inhibition of Klebsiella pneumoniae, Staphylococcus aureus and Enterococcus faecalis was shown by the essential oil.
La composición del aceite esencial de Dalea strobilacea Barneby (Fabaceae) obtenido por hidrodestilación de las partes aereas fue examinada por CG y CG/EM. beta-felandreno (44 por ciento) junto con alfa-pineno (18 por ciento) fueron los principales componentes del aceite esencial. La actividad antimicrobiana del aceite esencial fue evaluada contra ocho cepas bacterianas. El aceite esencial inhibió moderadamente el crecimiento de Klebsiella pneumoniae, Staphylococcus aureus y Enterococcus faecalis.
Assuntos
Antibacterianos/química , Antibacterianos/farmacologia , Bactérias , Fabaceae/química , Óleos Voláteis/química , Óleos Voláteis/farmacologia , Destilação , Enterococcus faecalis , Cromatografia Gasosa-Espectrometria de Massas , Klebsiella pneumoniae , Testes de Sensibilidade Microbiana , Staphylococcus aureusRESUMO
The vascular endothelium plays an essential role in the control of the blood flow. Pharmacological agents like quinone (menadione) at various doses modulate this process in a variety of ways. In this study, Q7, a 2-phenylamino-1,4-naphthoquinone derivative, significantly increased oxidative stress and induced vascular dysfunction at concentrations that were not cytotoxic to endothelial or vascular smooth muscle cells. Q7 reduced nitric oxide (NO) levels and endothelial vasodilation to acetylcholine in rat aorta. It also blunted the calcium release from intracellular stores by increasing the phenylephrine-induced vasoconstriction when CaCl2 was added to a calcium-free medium but did not affect the influx of calcium from extracellular space. Q7 increased the vasoconstriction to BaCl2 (10-3 M), an inward rectifying K+ channels blocker, and blocked the vasodilation to KCl (10-2 M) in aortic rings precontracted with BaCl2. This was recovered with sodium nitroprusside (10-8 M), a NO donor. In conclusion, Q7 induced vasoconstriction was through a modulation of cellular mechanisms involving calcium fluxes through K+ channels, and oxidative stress induced endothelium damage. These findings contribute to the characterization of new quinone derivatives with low cytotoxicity able to pharmacologically modulate vasodilation.
RESUMO
A variety of aminoisoquinoline-5,8-quinones bearing α-amino acids moieties were synthesized from 3-methyl-4-methoxycarbonylisoquinoline-5,8-quinone and diverse l- and d-α-amino acid methyl esters. The members of the series were evaluated for their cytotoxic activity against normal and cancer cell lines by using the (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) (MTT) assay. From the current investigation, structure-activity relationships demonstrate that the location and structure of the amino acid fragment plays a significant role in the cytotoxic effects. Moderate to high cytotoxic activity was observed and four members, derived from l-alanine, l-leucine, l-phenylalanine, and d-phenylalanine, were selected as promising compounds by their IC50 ranging from 0.5 to 6.25 µM and also by their good selectivity indexes (≥2.24).
Assuntos
Aminoácidos , Antineoplásicos , Citotoxinas , Neoplasias/tratamento farmacológico , Quinolonas , Aminoácidos/síntese química , Aminoácidos/química , Aminoácidos/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Citotoxinas/síntese química , Citotoxinas/química , Citotoxinas/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Neoplasias/metabolismo , Neoplasias/patologia , Quinolonas/síntese química , Quinolonas/química , Quinolonas/farmacologiaRESUMO
In the present study, we investigated sun protection factor and antioxidant properties of Parastrephia lepidophyla Cabr., Fabiana squamata Phil., Ephedra chilensis K.Presl., Lampaya medicinalis Phil., Baccharis tola Phil., and Azorella compacta Phil. The ethanol extracts were tested regarding their in vitro free radical scavenger ability and sun protection factor (SPF). Due to its antioxidant and photoprotective properties, B. tola is a promising candidate for use in cosmetic formulations. To evaluate the regenerative capacity of the B. tola extract, the planarian regeneration assay (Dugesia tigrina) was performed. Identification of phenolic compounds in B. tola, was performed by HPLC-ESI-MS/MS. Based on freeze-dried extracts of B. tola, a facial cream and a biphasic lotion with repairing tip action were formulated. These two formulations were evaluated by additional assays including organoleptic tests, measurement of pH, centrifugation and patch test to check a potential hypersensitivity (skin irritation) which can be induced by the products as well as a sensory survey. Stability studies, carried out over 12 months, prove that formulations were stable over time. It can be concluded that both products are innovative and shown solar protection, antioxidant and regenerative properties.
En el presente estudio, hemos investigado el factor de protección solar y propiedades antioxidantes de Parastrephia lepidophyla Cabr., Fabiana squamata Phil., Ephedra chilensis K.Presl., Lampaya medicinalis Phil., Baccharis tola Phil., y Azorella compacta Phil. Los extractos etanolicos fueron sometidos a ensayos como: evaluación in vitro de la actividad atrapadora de radicales libres y factor de protección solar (FPS). Debido a las propiedades antioxidantes y fotoprotectoras, B. tola es un candidato ideal para ser usado en formulaciones cosméticas. Se evaluó la capacidad regenerativa de B. tola en ensayos de planaria (Dugesia tigrina). Se identificó polifenoles por HPLC-ESI-MS/MS en B. tola. Se formularon una crema facial y una loción bifásica reparadora de puntas del cabello, en base a extractos liofilizados de Ñaca, a los cuales se le realizaron controles organolépticos, evaluación de pH, centrifugación, test de parche para evaluar la posible reacción de sensibilidad que pueden ocasionar los productos, comprobando que estos no producen irritación dérmica y posterior encuesta sensorial. Posteriormente, se realizaron estudios de estabilidad a lo largo de 12 meses, demostrando ser estable en el tiempo. Se puede concluir que ambos productos son innovadores y que muestran factor de protección solar, propiedades antioxidantes y regeneradoras.
Assuntos
Antioxidantes/química , Extratos Vegetais/química , Protetores Solares/química , Chile , Cromatografia Líquida de Alta PressãoRESUMO
Different concentrations of essential oil obtained from Acantholippia deserticola (Phil.ex F. Phil.) Moldenke were assessed against Chilean agricultural pests like Aleurothrixus floccosus (Maskell), Brevipalpus chilensis Baker, and Tetranychus urticae Koch. Thebioassays were carried out under laboratory conditions and both direct and residual applications were done through Potter precision spraytower test. The oil was obtained by steam distillation containing a rich fraction of alpha and beta-thujones (88.4 percent) and it shows marked toxic effects against pests. Indeed, a mortality of 82 percent and 89 percent was observed in both B. chilensis and T. urticae after 48 h whereas in A. floccosus over 97 percent of mortality was seen after 7 days. These results open the possibility to use essential oil from Acantholippia deserticola as natural pesticide.
Se evaluó el efecto a diferentes concentraciones de una solución de aceite esencial de Acantholippia deserticola sobre plagas agrícolas en Chile, tales como Aleurothrixus floccosus (Maskell), Brevipalpus chilensis Baker y Tetranychus urticae Koch. Los bioensayos fueron realizados mediante una torre de Potter en condiciones de laboratorio y las aplicaciones fueron directas y residuales. El aceite se obtuvo por hidrodestilación, el cual contenía una gran cantidad de alfa and beta-tuyonas (88.4 por ciento), mostrando marcados efectos tóxicos para A. floccosus, con un 97 por ciento de mortalidad después de 7 d y, para B. chilensis, y T. urticae, con una mortalidad de 82 por ciento y 89 por ciento respectivamente, después de 48 h. Estos resultados abren la posibilidad de usar aceite esencial de Acantholippia deserticola como pesticida natural.
Assuntos
Ácaros , Óleos Voláteis/farmacologia , Hemípteros , Praguicidas/farmacologia , Verbenaceae/química , Agricultura , Bioensaio , Monoterpenos/farmacologia , Controle Biológico de Vetores , Testes de ToxicidadeRESUMO
Acantholippia deserticola (Phil.ex F. Phil.) Moldenke is a Verbenaceae that has long been used in traditional medicine in Tarapacá (Chile) as an analgesic, anti-inflammatory and aphrodisiac agent. Sincé alpha - and beta -thujone were identified as the main constituents (88.4 percent) of the essential oil from this plant, we investigated its biological properties. The results show that the essential oil from Acantholippia deserticola decreased locomotive and rearing activity compared to control group rats, including those treated with diazepam, but the essential oil had no effects on head movements or grooming. The essential oil also had significant anxiolytic and antidepressant effects. This essential oil, therefore, has sedative, anxiolytic and antidepressant actions on the rat central nervous system.
Acantholippia deserticola es una Verbenaceae de uso en la medicina tradicional como analgésico, antiinflamatorio y afrodisíaco en la región de Tarapacá, Chile. En el aceite esencial se ha identificado alfa - and beta -tuyonas como principales constituyentes (88.4 por ciento) de esta planta, que ha llevado a investigar sus propiedades biológicas. Los resultados muestran que el aceite esencial de Acantholippia deserticola disminuye la locomoción y el levantamiento en dos patas, en comparación con el grupo control, incluido el tratado por el diazepam, pero el aceite esencial no tuvo efecto sobre la sacudida de cabeza y el acicalamiento. En ambas pruebas, se observa un efecto significativo del aceite esencial en los efectos ansiolíticos y antidepresivos, lo que indica que el aceite esencial tiene actividad sedante, ansiolítica y antidepresiva en el sistema nervioso central.
Assuntos
Animais , Ratos , Óleos Voláteis/farmacologia , Ansiolíticos/farmacologia , Antidepressivos/farmacologia , Verbenaceae/química , Óleos Voláteis/química , Medicina Tradicional , Monoterpenos/análise , Ratos Sprague-Dawley , Sistema Nervoso CentralRESUMO
We describe the biological activity of some furylbenzo- and naphthoquinones (furylquinones) on hepatocarcinoma cells and healthy rat liver slices. The effects of furylquinones on cancer cells (Transplantable Liver Tumor, TLT) were assessed by measuring cell death (membrane cell lysis); intracellular contents of ATP and GSH and the activity of caspase-3 were used to determine the type of cell death. Most of the furylquinones tested (at a concentration of 25 µg/ml) induced caspase-independent cell death but compound 4 had no cytotoxic effects. The levels of both ATP and GSH were severely affected by quinones 1, 2 and 5, while no effect was observed with compound 4. These cytotoxic properties of quinones are associated with physico-chemical properties as shown by the LUMO energies and lipophilicity. Interestingly, no cytotoxic effects of furylquinones were detected when the in vitro model of precision-cut liver slices (PCLS) was used. Indeed, although CYP2E1 activity was slightly affected, ATP and GSH levels as well as protein synthesis were not modified by furylquinones. Paracetamol, a well-known hepatotoxicant, reduced these parameters by more than 80% compared to control conditions. Taking into account the considerable incidence of adverse-effects induced by most current anticancer drugs, the selective cytotoxicity shown by compounds 1, 2 and 5, in particular that of 1, represents a safety factor that encourages the further development of these quinones as new drugs in cancer therapy.
Assuntos
Antineoplásicos/farmacologia , Quinonas/farmacologia , Trifosfato de Adenosina/metabolismo , Animais , Antineoplásicos/química , Antineoplásicos/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/enzimologia , Carcinoma Hepatocelular/patologia , Caspase 3/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Citocromo P-450 CYP2E1/metabolismo , Ensaios de Seleção de Medicamentos Antitumorais , Glutationa/metabolismo , Técnicas In Vitro , Fígado/efeitos dos fármacos , Fígado/enzimologia , Fígado/patologia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/enzimologia , Neoplasias Hepáticas/patologia , Masculino , Camundongos , Transplante de Neoplasias , Biossíntese de Proteínas/efeitos dos fármacos , Quinonas/química , Quinonas/uso terapêutico , Ratos , Ratos Wistar , SoftwareRESUMO
Data regarding tellurium (Te) toxicity are scarce. Studies on its metabolism, performed mainly in bacteria, underline a major role of reactive oxygen species (ROS). We investigated whether tellurite undergoes redox cycling leading to ROS formation and cancer cell death. The murine hepatocarcinoma Transplantable Liver Tumor (TLT) cells were challenged with tellurite either in the presence or in the absence of different compounds as N-acetylcysteine (NAC), 3-methyladenine, BAPTA-AM, and catalase. NAC inhibition of tellurite-mediated toxicity suggested a major role of oxidative stress. Tellurite also decreased both glutathione (GSH) and ATP content by 57 and 80%, respectively. In the presence of NAC however, the levels of such markers were almost fully restored. Tellurite-mediated ROS generation was assessed both by using the fluorescent, oxidation-sensitive probe dichlorodihydrofluorescein diacetate (DCHF-DA) and electron spin resonance (ESR) spectroscopy to detect hydroxyl radical formation. Cell death occurs by a caspase-independent mechanism, as shown by the lack of caspase-3 activity and no cleavage of poly(ADP-ribose)polymerase (PARP). The presence of gamma-H2AX suggests tellurite-induced DNA strand breaking, NAC being unable to counteract it. Although the calcium chelator BAPTA-AM did show no effect, the rapid phosphorylation of eIF2alpha suggests that, in addition to oxidative stress, an endoplasmic reticulum (ER) stress may be involved in the mechanisms leading to cell death by tellurite.
Assuntos
Carcinoma Hepatocelular/metabolismo , Morte Celular/efeitos dos fármacos , Neoplasias Hepáticas/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Telúrio/farmacologia , Trifosfato de Adenosina/metabolismo , Animais , Caspase 3/metabolismo , Linhagem Celular Tumoral , Glutationa/metabolismo , Humanos , Camundongos , Espécies Reativas de Oxigênio/metabolismoRESUMO
2-Euryfuryl-1,4-naphthoquinone C(1) and its 5- and 5,8-hydroxy derivatives C(2) and C(3), were tested for their cytotoxicity towards transplantable liver tumor (TLT) cells (a murine hepatoma cell line) in the absence and in the presence of vitamin C. Cell death, caspase-3 activity and two metabolic end-points, namely the intracellular content of ATP and glutathione (GSH), were employed to evaluate their cytotoxicity. In a range of concentration from 0 to 10 microg/ml C(1) and C(3) were non toxic against TLT cells, while compound C(2) killed about 50% of cells by necrosis. Interestingly, the presence of vitamin C did not enhance the cytolysis of C(2), but its addition exacerbated the effects of the three compounds on both ATP and GSH contents, the two metabolic end points selected in our study. Our assumption is that the electron donor effect of the peri-hydroxyl substituents on euryfurylnaphthoquinones and the hydrogen bond between the peri-hydroxy and quinone carbonyl groups influence the electron-acceptor capability of the quinone nucleus and thus modifies the electron transfer from ascorbate to the electroactive quinone nucleus. The combination of euryfurylnaphthoquinones with vitamin C may be of potential clinical interest, because cancer cells accumulate vitamin C, they are sensitive to an oxidant insult and they depend on glycolysis (ATP formation) for their survival.