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ABSTRACT: The cytotoxicities of nine diterpene polyesters obtained from Euphorbia species were assayed by measuring their effects on the growth of Vero cells. Their antiviral effects on the multiplication of Herpes simplex virus type 2 (HSV-2) were studied by using the virus yield reduction method in cell cultures. With the exception of the strongly cytotoxic 2alpha,5alpha,14beta-triacetoxy-3beta-benzoyloxy-8alpha,15beta-dihydroxy-7beta-isobutanoyloxy-9alpha-nicotinoyloxyjatropha-6(17),11E-diene (CC(50) 3.5 microg/ml), all the tested diterpenes exhibited a pronounced or moderate anti-herpes virus effect (IC(50) values between 2.5 and 8.3 microg/ml). The observed HSV-2 inhibitory activities were not associated with virucidal effects.
Planta Medica 11/2001; 67(7):672-4. · 2.15 Impact Factor
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ABSTRACT: The combined antiviral effects of some benzo[a]phenothiazines and 9-[2-hydroxy(ethoxy)methyl]guanine (acycloguanosine, acyclovir, ACV) on the multiplication of herpes simplex virus type 2 (HSV-2) were studied using Vero cells. The antiviral effect of ACV on a wild strain of HSV-2 was enhanced in the presence of 5-oxo-5H-benzo[a]phenothiazine and 6-methyl-5-oxo-5H-benzo[a]phenothiazine in a yield reduction test. A mathematical formula was used to interpret the drug interaction and a synergistic effect was found with a combination of ACV and benzo[a]phenothiazines. The effect of simultaneous application of two benzo[a]phenothiazines on the multiplication of HSV-2 strain during serial passages was also investigated. The combinations of 5-oxo-5H-benzo[a]phenothiazine or 6-methyl-5-oxo-5H-benzo[a]phenothiazine with ACV at a low concentration using serial passages of a plaque-purified ACV sensitive HSV-2 strain, reduced the infective virus population. A similar effect was also found on the activity of other benzo[a]phenothiazine derivatives. When the two most effective derivatives of 5-oxo-5H-benzo[a]phenothiazine or 6-methyl-5-oxo-5H-benzo[a]phenothiazine were simultaneously used with ACV against a wild type HSV-2 strain during consecutive passages, the infective virus titres were decreased, but their effect was only moderate. These results suggest that a combination of some benzo[a]phenothiazines with ACV might enhance their antiviral activity probably by reduction of the mutagenic rate in the virus populations.
International Journal of Antimicrobial Agents 08/2001; 18(1):67-72. · 4.13 Impact Factor
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ABSTRACT: The combined antiviral effects of some flavonoid compounds and acycloguanosine (acyclovir, Zovirax) were studied on the multiplication of herpes simplex virus types 1 and 2 in HEp-2 cells and on pseudorabies (Aujeszky) virus in chick embryo fibroblast cells by the yield reduction method. The flavonoids quercetin, quercitrin (quercetin-3-L-rhamnoside) and apigenin exhibit antiviral activity against these herpesviruses, and acyclovir is currently one of the most effective antiherpetic agents. In these studies, the simultaneous application of flavonoids with acyclovir resulted in an enhanced antiviral activity. A mathematical formula was used to interpret the drug interaction, resulting in FIC (fractional inhibitory concentration) indices. Meaning a synergic interaction, all combinations exhibited synergy, FIC values of 0.6-0.8 being commonly observed.
Acta microbiologica Hungarica 02/1992; 39(2):137-47.
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ABSTRACT: Several phenolic glycosides, i.e. acteoside, desrhamnosyl acteoside, and purpureaside A, B and C, exerted weak antibacterial effects on Escherichia coli. Acteoside had antiplasmid effects, including F'lac plasmid elimination, and inhibited kanamycin resistance transfer in E. coli. Acteoside, desrhamnosyl acteoside and purpureaside A displayed antiviral effect on Aujeszky virus. All of the phenolic glycosides decreased some human leucocyte functions, including rosette formation, mitogen-induced blast transformation and phagocytic activity in vitro. The purpureaside C had significant proinflammatory action, however, other phenolic glycosides showed neither proinflammatory nor antiinflammatory effect on carrageenin-induced inflammation in vivo.
Acta microbiologica Hungarica 02/1989; 36(4):425-32.
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ABSTRACT: A newly synthetized rutin derivative, rutin-N-mustard, showed a marked antiproliferative effect on NK/Ly ascites tumour cells in vivo. When administered i.p. or i.v., this compound increased the survival time of the animals, but oral administration had no such effect. The drug was not able to kill the tumour cells, since the chromium release from the rutin-N-mustard-treated tumour cells was the same as in the case of the controls. Tumour growth was completely inhibited in the animals when the cells were pretreated with 100 mg/kg rutin-N-mustard before transplantation. The results also showed that rutin-N-mustard has little effect on the xenogenization of NK/Ly tumour cells. We presume that the antiproliferative action of rutin-N-mustard is due to its alkylating activity.
International Journal of Cancer 01/1983; 30(6):767-71. · 5.44 Impact Factor
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ABSTRACT: All human, simian, bovine and avian adenovirus types tested so far and the canine hepatitis virus induce interferon production in chick cells. This finding indicated this property to be characteristic for viruses belonging to the adenovirus group. Trypsin treatment, which had no effect upon the infectivity, diminished or eliminated the interferon-inducing abilities of crude adenoviruses, and thus the need for a trypsin-sensitive protein in interferon induction was suggested. T antigen and interferon were formed simultaneously in chick embryo fibroblast cells infected with human adenovirus type 12, and therefore the adenovirus-specific T antigen was resistant to the action of endogenous interferon synthetized by the same cells. In chicks inoculated with human types, the appearance of interferon was biphasic: an 'early' and a 'late' interferon could be demonstrated with maximum titre 4 and 10 hr, respectively, after virus infection. In chicks infected with adenoviruses, first interferon production and then a decreased primary immune response to sheep red blood cells was observed. It was assumed that in adenovirus-infected chicks the interferon produced by viral stimulus resulted in a transient immunosuppression.
Postgraduate Medical Journal 03/1979; 55(640):128-34. · 1.94 Impact Factor
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ABSTRACT: Among the four flavonoids tested quercetin and morin proved to be significantly effective against lethal Mengo virus-induced encephalitis in mice when the drugs were adminsitered orally (p.o.). With subcutaneous (s.c.) administration all four drugs failed to prevent mortality in the infected mice. Quercetin produced maximum protective response in intraperitoneally (i.p.) or intranasally (i.nas.) infected mice when administered twice daily at doses of 20 mg/kg for a period of not less than four days. Single injections of the full daily dose of drug failed to prevent deaths in mice. Treatment must be begun at the time of, or prior to, virus inoculation. Delayed initiation of treatment was ineffective in preventing mortality.
Archives of Virology 02/1978; 57(3):255-60. · 2.11 Impact Factor
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Annals of the New York Academy of Sciences 04/1977; 284:358-64. · 3.15 Impact Factor
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ABSTRACT: Human adenovirus types 6, 8, and 12 were immunosuppressive in chickens. A single intravenous injection of adenoviruses markedly depressed the 19S hemolytic plaque-forming cell response in the spleen to the immunization with sheep red blood cells. Hemagglutinin production was also decreased in adenovirus type 6-infected chickens. Adenoviruses caused a transient immunosuppression in chickens which could be detected 2 to 3 days after the virus infection, and no depressive effect was found 16 to 20 days after virus injection. The possible mechanism of immunosuppression observed is discussed.
Infection and Immunity 02/1973; 7(1):22-8. · 4.16 Impact Factor
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Acta virologica 12/1970; 14(6):453-8. · 0.68 Impact Factor
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Journal of General Virology 02/1970; 7(2):153-8. · 3.36 Impact Factor
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Journal of General Virology 04/1969; 4(2):169-76. · 3.36 Impact Factor
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Acta virologica 02/1969; 13(1):71-3. · 0.68 Impact Factor
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Acta microbiologica Academiae Scientiarum Hungaricae 02/1968; 15(3):223-7.
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Acta microbiologica Academiae Scientiarum Hungaricae 02/1966; 13(2):113-8.
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Acta microbiologica Academiae Scientiarum Hungaricae 12(4):327-35.
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ABSTRACT: The efflux pump of multidrug resistant mdr cells have different sensitivities to some stereoisomeric forms of CNS-active compounds. The ABC transporters of mdr cells were more sensitive to (-)butaclamol than to its stereoisomeric counterpart (8), which may function to alter the membrane structure. We suppose that the drug-accessible membrane structure possesses an important role in the induction (or prevention) of apoptosis. Therefore the apoptosis-inducing effect of three stereoisomeric pairs was studied on mouse lymphoma cells. In these experiments levo- and dextromepromazine had similiar effects. The cis- and trans-clopenthixol were less effective in apoptosis induction than the 12H-benzo(a)-phenothiazine used as a positive control. The effect of stereoisomeric pairs on induced apoptosis was studied when the cells were exposed to the stereoisomers for 60 minutes before subjection apoptosis induction by benzo(a)phenothiazine, a well-known apoptosis inducer. Then the pretreated cells were exposed to 12H-benzo(a)-phenothiazine for 60 minutes. The samples were washed and incubated for 24 hours. The cells were stained with annexin-V-FITC and propidium iodine and investigated by flow cytometry. The mdr cells with increased membrane integrity may result in the preferential killing of multidrug resistant cancer cells in the presence of some stereoisomers.
Anticancer research 21(4A):2709-12. · 1.73 Impact Factor
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N Motohashi,
T Kurihara,
H Wakabayashi,
M Yaji, I Mucsi,
J Molnár,
S Maruyama,
H Sakagami,
H Nakashima,
S Tani,
Y Shirataki,
M Kawase
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ABSTRACT: Russian green sweet pepper (Anastasia Green) was successively extracted with hexane, acetone, methanol and 70% methanol and the extracts were further separated into a total of twenty fractions by silica gel or ODS column chromatographies. The biological activities of these extracts and fractions were compared. The extracts and fractions showed higher cytotoxic activity against two human oral tumor cell lines than against normal human gingival fibroblasts, suggesting their tumor-specific action. Several fractions [H3, H4, A4] reversed the multidrug resistant gene (MDR1) against L5178 mouse T-cell lymphoma more effectively than (+/-) verapamil (positive control). All extracts and fractions showed no anti-human immunodeficiency virus (HIV) nor anti-Helicobacter pylori activity. These data suggest the medicinal importance of an Anastasia Green extract.
In vivo (Athens, Greece) 15(5):437-42. · 1.17 Impact Factor
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J Molnar, I Mucsi,
J Nacsa,
A Hevér,
N Gyémánt,
K Ugocsai,
P Hegyes,
St Kiessig,
D Gaal,
H Lage,
A Varga
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ABSTRACT: The efficiency of chemotherapy is often decreased by the development of resistance of cancer cells to cytostatic drugs. This phenomenon is in most cases caused by the activity of the various ABC transporters, multidrug-resistance (MDR) gene-encoded p-glycoproteins, that pump anticancer drugs out of the cells. The inhibition of the activities of the MDR proteins MDR1 and MRP was investigated via the administration of two new organosilicon compounds, alis-409 and alis-421. The study was focused on the inhibition of MDR by blocking the ADR1 gene expression and through the inhibition of the pump-function of mdr-p-glycoprotein, in human breast cancer cell lines expressing mrp and prostate cancer cell line (PC-3). Apoptosis induction and the interaction between epirubicin and the silicon-substituted compounds were studied in human MDR-1 gene-transfected mouse lymphoma and its parent cell line, Colo320/MDR-LRP and sensitive subline Colo205, by means of rhodamine 123 accumulation. The activity of MRP1 p-glycoprotein was studied in human breast cancer cell lines such as HTB-26/MRP1 and two MRP-negative breast cancer cell lines, T47D and MCF7, by carboxyfluorescein accumulation, and on a stomach cancer cell line. The activity of MRP in 257P/MDR and its drug-sensitive derivative were studied in human stomach cancer cells by daunorubicin accumulation in a flow cytometer. The two representative organosilicon derivatives, alis-409 and alis-421, showed antiproliferative effects without apoptosis induction. The drug accumulation in the human MDR1 gene-transfected mouse lymphoma cells was increased without down-regulation of the MDR1 gene expression tested by RT-PCR assay. The rhodamine uptake was increased in L5178/MDR1 and Colo320/MDR1-LRP, but not drug-sensitive human breast cancer MCF-7 and T47D, and L5178 mouse lymphoma parent cells in the presence of alis-409 and alis-421. The MRP-mediated carboxyfluorescein accumulation in HTB-26/MRP human breast cancer cells and daunorubicin accumulation in human stomach cancer cells 257P/MDR were not modified by these alis compounds. A synergistic interaction between epirubicin and the silicon-substituted resistance modifiers was found only in MDR1-mediated MDR in the case of colo-320/MDR1-LRP cells and mouse lymphoma cells transfected with the human MDR1 gene. The results indicate that the organosilyl derivatives specifically act on MDR1 p-glycoprotein 170. The alis compounds act on pgp170 in a way which is similar to verapamil isomers.
Anticancer research 24(2B):865-71. · 1.73 Impact Factor
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N Motohashi,
M Kawase,
Y Shirataki,
S Tani,
S Saito,
H Sakagami,
T Kurihara,
H Nakashima,
K Wolfard, I Mucsi,
A Varga,
J Molnár
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ABSTRACT: Fractionated extracts of Feijoa peels were studied for cytotoxic activity, anti-human immunodeficiency virus (HIV) activity and antibacterial activity. Two most cytotoxic fractions A3 of acetone extract and M2 of methanol extract had potent inhibitory activity against Gram-positive and Gram-negative bacteria as well as fungi tested. Fraction A4 of acetone extract showed multidrug resistance (MDR)-reversal activity comparable with that of verapamil (positive control). These results indicate the therapeutic value of Feijoa peel extracts as potential antimicrobial and MDR-modulating agents.
Anticancer research 20(6B):4323-9. · 1.73 Impact Factor
