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B Rada

Publications and source records attributed to B Rada.

At least 19 recordsLinked to original sources
PubMed1990

Antiviral activities of pyrimidine nucleoside analogues: some structure--activity relationships.

Seventeen nucleoside derivatives (derived from arabinosylcytosine, resp. cytidine, 5-fluorouracil and uracil) were tested by agar-diffusion plaque-inhibition test for their antiviral activity with herpes simplex, vaccinia, fowl plague, Newcastle disease and western equine encephalomyelitis viruses. The highest antiviral activity against DNA viruses exhibited arabinosylcytosine, N4-acylarabinosylcytosines, arabinosylthiouracil, cyclocytidine and its 5'-chloroderivative. RNA viruses were inhibited by 5-fluorouridine only, whereas other tested compounds were ineffective or showing marginal activity only. By search for relationship between chemical structure and antiviral activity a tendency was found of higher antiviral activity at lower lipophilicity. This is probably due to better transport of the studied compounds into cell. The chemical structure, however, is the main reason of antiviral activity.

Animals↗
PubMed1987

Rapid method for the detection of synergism in combinations of antiviral substances.

The plaque inhibition method was modified in order to evaluate the effectiveness of various combinations of antiviral substances. One substance (A) diffuses from the centre of cell culture, the other (B) is incorporated into the agar overlay at subinhibitory concentration. The inhibitory effect of the combination (A + B) is demonstrated by the increase in size of the inhibitory zone in comparison with the control inhibitory zone produced by the substance A alone. The ratio of the diameter of the inhibitory zone with substance combination (A + B) to the diameter of single drug control zone (substance A) serves as index DI (degree of interaction). Quantitative evaluation of the degree of potentiation using isobolograms showed that DI greater than 1.5 indicate a synergistic effect of the respective combinations. This inexpensive method can serve for rapid selection of suitable combinations out of number of substances. Model experiments were performed with combinations of selected inhibitors of virus replication.

Animals↗
PubMed1984

Site of action of N,N'-bis(methylisatin-beta-thiosemicarbazone)-2-methylpiperazine in the vaccinia virus replication cycle.

N,N'-Bis(methylisatin-beta-thiosemicarbazone)-2-methylpiperazine inhibits late function or synthesis of a late component in the replication cycle of vaccinia virus. The kinetics of formation of the component sensitive to the inhibition with N,N'-bis(methylisatin-beta-thiosemicarbazone)-2-methylpiperazine precedes that of appearance of infectious virus by 30 min. The finding is in accord with the site of action of unsubstituted isatin-beta-thiosemicarbazone.

Antiviral Agents↗
PubMed1984

The role of cell type in transport and metabolic conversion of antiviral substances.

The transport and metabolic conversion of 6-azauridine differed when compared in HeLa and chick embryo (CE) cells. The values of 9-(S)-(2, 3-dihydroxypropyl) adenine transported into the cells were found different for ZP cells (rabbit lung cell line), HeLa and CE cells. These differences were less expressed if relating the values of cellular uptake and metabolic conversion to the cell volume of the respective cell type. The differences seem to play a role in quantitation of the antiviral potency of the compounds in different host cells.

Animals↗
PubMed1983

Transport of antiviral agent 9-(S)-(2,3-dihydroxypropyl) adenine to animal cells.

Transport properties of 9-(S)-(2,3-dihydroxypropyl) adenine (DHPA) in cell cultures were studied. Transport of DHPA into chick embryo (CE), ZP (a cell line derived from rabbit lungs) and HeLa cells reached equilibrium values after 10 min incubation. The concentration of intracellular DHPA varied from 30 to 50 per cent of that in the medium. DHPA transport was only slightly affected during the lag phase of vaccinia virus replication. The opinion that DHPA is transported into the cell by facilitated diffusion, is supported 1) by the data on DHPA transport as a function of temperature and extracellular concentration, 2) by evidence of countertransport, 3) by temperature-dependent exit of DHPA, 4) by specific inhibition of DHPA transport in the presence of adenosine and deoxyadenosine and 5) by the fact that intracellular concentration of DHPA in equilibrium does not reach the concentration of DHPA in the medium. V and KM values varied in the range of 2-17 pmoles/min per 10(6) cells and 4-7 microM, respectively.

Adenine↗
PubMed1980

Virus inhibitory effect of combination of 9-(S)-(2,3-dihydroxypropyl) adenine and 6-azauridine.

Combination of 9-(S)-(2,3-dihydroxypropyl)adenine [(S)-DHPA] and 6-azauridine (AzUrd) is highly active in the selective inhibition of vaccinia virus in chick embryo cell culture. Synergic effect of this combination of compounds was not encountered in HeLa cell culture. Of the 17 analogues related to DHPA studied in this paper, 3 showed medium activity against vaccinia virus, but none of them was as effective as (S)-DHPA in combination with AzUrd.

Adenine↗
PubMed1980

Characteristics of the antiviral effect of 9-(S)-(2, 3-dihydroxypropyl)adenine.

9(S)-(2,3-Dihydroxypropyl)adenine (DHPA) at 1--3 mg/ml completely inhibited the replication of vaccinia virus in ZP cells; the analogue did not inactivate the virus. Formation of a virus component sensitive to DHPA preceded by 2 hr the formation of infectious vaccinia virus. It seems likely that the component inhibited by DHPA is viral mRNA. The virus inhibitory effect was not reverted by numerous nucleotides, nucleosides or amino acids. DHPA was not metabolized during the latent period of vaccinia virus replication cycle either in uninfected ZP or chick embryo cell cultures.

Adenine↗
PubMed1979

Antiviral activity of benzothiazole and benzothiazolinethione derivatives in cell cultures.

The virus inhibitory activity of benzothiazole, benzothiazolinethione and naphthothiazole derivatives was tested with vaccinia virus, Newcastle disease virus (NDV) and western equine encephalomyelitis (WEE) virus in the agar-diffusion plaque-inhibition test. Among 58 compounds examined, 5 showed medium activity and selectivity with vaccinia virus. The highest selective effect was found with 3-(2-ethylthio-6-benzothiazolylaminomethyl)-2-benzothiazolinethione. A much lower inhibitory effect was observed with several derivatives against WEE virus. One derivative (2-mercaptobenzothiazole) showed a low inhibitory effect against NDV.

Chemical Phenomena↗
PubMed1977

Antiviral action and selectivity of 6-azauridine.

6-Azauridine (AzUrd) is a broad-spectrum antimetabolite that inhibits both DNA and RNA virus multiplication. Prior work indicated that several AzUrd-sensitive viruses induced an increase in the level of uridine kinase, and this might explain the selective activity of AzUrd on such viruses. Present studies compared AzUrd sensitive and resistant viruses with respect to their orotic acid pathways by labeling cells with [14C]-orotic acid during the latent period of viral infection. No differences were detected by this method with either vaccinia, Newcastle disease, or vesicular stomatitis viruses. AzUrd inhibits transport of orotic acid into the cell by 30%, while incorporation of orotic acid into cellular RNA is inhibited by 50% (taking into consideration the 30% already noted) when the highest concentration of antimetabolite is used. This suggests that, in addition to blocking orotidylic acid decarboxylase, AzUrd may act on some other site (sites) of action in the inhibition of virus multiplication.

Antiviral Agents↗
PubMed1977

Antiviral effect of tebrofen.

Tebrofen inhibited the replication of western equine encephalomyelitis (WEE) virus in multicycle experiments in chick embryo cell cell cultures. The compound did not inhibit the replication of vaccinia and Newcastle disease viruses.

Animals↗
PubMed1976

Inhibition of Newcastle disease virus replication by 6-azauridine. II. Combination of 6-azauridine and adenine derivatives.

Twenty-five metabolites (purines, pyrimidines, nucleosides and nucleosides) were tested for their simultaneous action with 6-azauridine (AzUrd) in inhibition of Newcastle disease virus (NDV) replication. With the exception of deoxyadenosine and cyclic AMP all natural adenine derivatives exerted a synergic effect with AzUrd like ATP. Glutamine in combination with AzUrd did not inhibit NDV replication. The inhibitory effect of the combination of AzUrd and adenine derivatives was reversible by guanosine, uridine and cytidine but not by orotic acid or orotidylic acid.

Adenine↗
PubMed1976

Inhibition of Newcastle disease virus replication by 6-azauridine. I. Inefficacy of purified uridine kinase, effect of adenosine-5'-triphosphate.

As distinct from cell-free extracts prepared from tumour cells, partially purified uridine kinase prepared from the same cells was not effective in 6-azauridine (AzUrd) inhibition of Newcastle disease virus (NDV) replication. This showed that uridine kinase was not the effective component of cell-free extracts. Adenosine-5'-triphosphate (ATP) was found to exert a synergic effect in combination with AzUrd in the inhibition of NDV replication.

Adenosine Triphosphate↗