Chemotherapie der Herpes-Infektion mit neuen 5-Alkyluracildesoxyribosiden

Gauri, K. K.; Malorny, G.

doi:10.1007/bf00537395

Cited by 45 publications

(13 citation statements)

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“…Several nucleoside analogues have been used in the therapy of herpes simplex virus (HSV) infection (Gauri, 1979;Gauri & Walter, 1973;Gauri & Malorny, 1967;Kaufmann & Heidelberger, 1964;Kaufmann et aL, 1962;Schabel, 1968). Some nucleoside analogues which are efficiently phosphorylated by cellular kinases and are incorporated into DNA in proliferating cells and tissues show cytotoxic effects in uninfected cells (Gauri et al, 1976;Kit, 1976).…”

Section: Introductionmentioning

confidence: 99%

Differential Incorporation of Thymidylate Analogues into DNA by DNA Polymerase and by DNA Polymerases Specified by Two Herpes Simplex Viruses

Kowalzick

Gauri

Spadari

et al. 1982

Journal of General Virology

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SUMMARYSeveral triphosphates (TP) of 5-substituted deoxyuridine (dU), like 5-ethyl (Et), 5-n-propyl (n-Pr), 5-iso-propyl (iso-Pr), 5-n-hexyl (n-Hx), and 5-trifluorothymidine (Fa-dT) were used as substrates for HeLa DNA polymerase a and for two herpes simplex virus (HSV)-coded DNA polymerases isolated from HeLa cells infected with HSV-1, strain C42 (wild-type), or its mutant resistant to phosphonoformate (PFAr). All polymerases were purified up to the DNA-cellulose column step and they showed comparable specific activities. The incorporation into DNA studied with all the alkyl analogues of dUTP is several times higher with the virus enzymes than with DNA polymerase a. The DNA polymerase of the mutant virus incorporates dUTP analogues to a lower extent than the wild-type polymerase. The two virus enzymes also differ in the K m and Vma X values for different substrates, indicating that the mutation to PFA r has affected the structure of the virus DNA polymerase. Surprisingly, all three enzymes use Fa-dTTP as substrate for DNA synthesis to an equal but limited extent.

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Section: Introductionmentioning

confidence: 99%

Differential Incorporation of Thymidylate Analogues into DNA by DNA Polymerase and by DNA Polymerases Specified by Two Herpes Simplex Viruses

Kowalzick

Gauri

Spadari

et al. 1982

Journal of General Virology

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“…Accordingly, PrUdR, the antiviral properties of which were first mentioned by Gauri and Malorny (10), could be considered as a selective inhibitor of herpes simplex virus.…”

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confidence: 99%

“…nosyl-5-methylcytosine (1,8,11), and 5-ethyl-, 5-vinyl-, 5-propyl-and 5-allyl-2'-deoxyuridine (3,7,10), have been shown to inhibit the replication of herpes simplex virus (or varicella-zoster virus [9]) at doses which did not adversely affect the growth of the (uninfected) host cells. Whereas 5-iodo-2'-deoxycytidine, 5-bromo-2'-deoxycytidine, 5-ethyl-2'-deoxyuridine, and 1-fl-D-arabinofuranosylthymine were also reported as being active against vaccinia virus (7,8,15,16), other TdR analogs such as 5-iodo-5'-amino-2'-5'-dideoxyuridine (14), 5-methylamino-and 5-methoxymethyl-2'-deoxyuridine (2, 18) proved specifically active against herpes simplex virus.…”

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confidence: 99%

5-Propyl-2'-deoxyuridine: a specific anti-herpes agent

Clercq¹,

Descamps²,

Shugar³

1978

Antimicrob Agents Chemother

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“…The activity of 5-ethyl-2'-deoxyuridine (EdU) against infection with herpes simplex virus (HSV) was first recognized in 1967 (13). In vitro testing by reduction in cytopathic effect has identified the mean 50% inhibitory dose against HSV type 1 (HSV-1) and HSV type 2 (HSV-2) to be 0.3 to 0.5 FLg/ml in primary rabbit kidney cells (8) and BHK-21 cells (22).…”

mentioning

confidence: 99%

Comparison of topically applied 5-ethyl-2'-deoxyuridine and acyclovir in the treatment of cutaneous herpes simplex virus infection in guinea pigs

Spruance¹,

Freeman²,

Sheth³

1985

Antimicrob Agents Chemother

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Three percent 5-ethyl-2'-deoxyuridine (EdU) in an aqueous cream base was compared with 5% acyclovir (ACV) in polyethylene glycol ointment and 3% EdU in 95% dimethyl sulfoxide (DMSO) for efficacy in the topical treatment of an experimental dorsal cutaneous herpes simplex virus type 1 infection in guinea pigs. Topical ACV treatment reduced the mean lesion number by 15%, the lesion area by 32%, and the lesion virus titer by 60% when compared with measurements at contralateral sites treated with the vehicle alone. Application of 3% EdU cream was more beneficial, effecting reductions of 29, 44, and 68% in the same measurements. EdU in DMSO was even more effective, reducing the lesion measurements by 39, 60, and 90%, respectively. The penetration of EdU and ACV through guinea pig skin was compared in single-chamber diffusion cells. In the aqueous cream, EdU readily penetrated excised skin and exhibited rates of flux 10-fold greater than those shown by ACV in ointment formnulation (0.56 versus 0.05 pg/cm2 per h; P = 0.05). The flux of EdU in DMSO was 3.39 jig/cm2 per h, six times higher than the flux in the cream vehicle. EdU was more effective than ACV in this experimental animal model, most likely due to better percutaneous drug delivery of EdU from the cream and DMSO vehicles.The activity of 5-ethyl-2'-deoxyuridine (EdU) against infection with herpes simplex virus (HSV) was first recognized in 1967 (13). In vitro testing by reduction in cytopathic effect has identified the mean 50% inhibitory dose against HSV type 1 (HSV-1) and HSV type 2 (HSV-2) to be 0.3 to 0.5

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Chemotherapie der Herpes-Infektion mit neuen 5-Alkyluracildesoxyribosiden

Cited by 45 publications

References 1 publication

Differential Incorporation of Thymidylate Analogues into DNA by DNA Polymerase and by DNA Polymerases Specified by Two Herpes Simplex Viruses

Differential Incorporation of Thymidylate Analogues into DNA by DNA Polymerase and by DNA Polymerases Specified by Two Herpes Simplex Viruses

5-Propyl-2'-deoxyuridine: a specific anti-herpes agent

Comparison of topically applied 5-ethyl-2'-deoxyuridine and acyclovir in the treatment of cutaneous herpes simplex virus infection in guinea pigs

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