The effect of the antiherpesvirus drug 5-methoxymethyl-2′-deoxyuridine on the humoral immune response in vivo

Bt, Rouse; La, Babiuk; Vs, Gupta

doi:10.1139/m77-158

Cited by 7 publications

(3 citation statements)

References 7 publications

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“…In addition, some tend to have poor aqueous solubility [28]. MMUdR is a unique nucleoside antimetabolite since it has been found to be nontoxic to lymphoid functions in vitro [3] and devoid of immu nosuppressant activity in vivo [31]. The re sults of studies reported in this paper indi cate that 2 and 5% MMUdR in either PVA or ABT were effective in the treatment of herpes keratitis.…”

Section: Discussionmentioning

confidence: 83%

Comparative Efficacy of 5-Methoxymethyl-2’-Deoxyuridine, 9β-D-Arabinofuranosyladenine and 5-Iodo-2’-Deoxyuridine in the Treatment of Experimental Herpes Simplex Keratitis

Meldrum¹,

Gupta²,

Babiuk³

1980

Chemotherapy

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The relative efficacy of 5-methoxymethyldeoxyuridine (MMUdR), adenine arabinoside (Ara-A), 5-iododeoxyuridine (IUdR) and the combination of MMUdR and Ara-A in the treatment of experimental herpes simplex keratitis was investigated in rabbits. Treatment was initiated either at 4 or 24 h post virus inoculation. The parameter used to evaluate effectiveness was lesion size. Each eye was graded daily for the first 5 days and on alternate days thereafter to day 11. At concentrations of 2 or 5% both MMUdR and Ara-A were found to have potent antikeratitis activity. At 5% concentration, Ara-A provided essentially the same protection against herpes keratitis as 0.1% IUdR, while MMUdR was slightly less effective. The simultaneous application of 2% MMUdR and 2% Ara-A in combination was more effective than 5% MMUdR alone and was as effective as 5% Ara-A or 0.1% IUdR in controlling the viral keratitis.

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Section: Discussionmentioning

confidence: 83%

Comparative Efficacy of 5-Methoxymethyl-2’-Deoxyuridine, 9β-D-Arabinofuranosyladenine and 5-Iodo-2’-Deoxyuridine in the Treatment of Experimental Herpes Simplex Keratitis

Meldrum¹,

Gupta²,

Babiuk³

1980

Chemotherapy

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“…5-Methoxymethyl-2' -Deoxyuridine 5-Methoxymethyl-2'~deoxyuridine (MMdUrd) was synthesized by BUBBAR and GUPTA (1970). MMdUrd does not appear to be immunosuppressive ROUSE et al 1977) and the basis for its selectivity and its mechanism of action are unknown. At 100 times the antiviral concentration, MMdUrd did not cause host cell toxicity .The analog was ineffective against vaccinia virus, murine cytomegalovirus, equine rhinopneumonitis, and feline pneumonitis viruses as well ).…”

Section: E-5-(2-bromovinyl)-2'-deoxyuridine (Bvdurd)mentioning

confidence: 99%

Chemotherapy of Viral Infections

Jones¹

1982

Handbook of Experimental Pharmacology

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“…It is devoid of toxicity to lymphoid functions in vitro (2), is non-immunosuppressive in vivo (26), and is effective in the treatment of keratitis in animals (20 In each experiment, toxicity controls (containing test compound and medium only), cell controls (containing medium only), and virus controls (containing virus and medium only) were also run simultaneously. The percentage ofinhibition (calculated from the reduction in the number of plaques) at each concentration of the compound was determined.…”

mentioning

confidence: 99%

Combination chemotherapy: interaction of 5-methoxymethyldeoxyuridine with adenine arabinoside, 5-ethyldeoxyuridine, 5-iododeoxyuridine, and phosphonoacetic acid against herpes simplex virus types 1 and 2

Ayisi¹,

Gupta²,

Meldrum³

et al. 1980

Antimicrob Agents Chemother

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The antiviral activity of 5-methoxymethyl-2'-deoxyuridine (MMUdR) was compared with that of 5-iodo-2'-deoxyuridine (IUdR), 5-ethyl-2'-deoxyuridine (EtUdR), adenine arabinoside (Ara-A), and phosphonoacetic acid (PAA) against herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2). MMUdR was more potent than Ara-A and PAA but less active than EtUdR and IUdR against HSV-1 in rabbit kidney (RK-13) cells. In Vero cells, the antiviral activities of MMUdR, Ara-A, and PAA against HSV-1 were of the same order of magnitude. The antiviral potency against HSV-2 varied with the strain of virus used. All strains of HSV-2 were markedly inhibited by EtUdR and IUdR and to a lesser degree by PAA. However, considerable variation was noticed in the susceptibility of HSV-2 strains to Ara-A and MMUdR. Interaction of MMUdR with Ara-A, EtUdR, IUdR, and PAA was investigated by the method of response isobolograms. MMUdR showed synergistic activity in combination with Ara-A and PAA but antagonistic activity in combination with EtUdR and IUdR against herpesviruses. Minimum toxic dose (concentration required to produce definite evidence of microscopic cytotoxicity in rapidly growing RK-13 cells) was determined for each compound and was found to be 512, 172, 64, 8, and less than 0.5 microgram/ml for MMUdR, PAA, Ara-A, EtUdR, and IUdR, respectively. MMUdR was found to have the maximum antiviral index against HSV-1 (512) and HSV-2 strains X-265 (102) and ATCC (85). Antiviral index was defined as the minimum toxic dose divided by the dose that reduced plaque numbers by 50%.

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The effect of the antiherpesvirus drug 5-methoxymethyl-2′-deoxyuridine on the humoral immune response in vivo

Cited by 7 publications

References 7 publications

Comparative Efficacy of 5-Methoxymethyl-2’-Deoxyuridine, 9<i>β</i>-<i>D</i>-Arabinofuranosyladenine and 5-Iodo-2’-Deoxyuridine in the Treatment of Experimental Herpes Simplex Keratitis

Comparative Efficacy of 5-Methoxymethyl-2’-Deoxyuridine, 9<i>β</i>-<i>D</i>-Arabinofuranosyladenine and 5-Iodo-2’-Deoxyuridine in the Treatment of Experimental Herpes Simplex Keratitis

Chemotherapy of Viral Infections

Combination chemotherapy: interaction of 5-methoxymethyldeoxyuridine with adenine arabinoside, 5-ethyldeoxyuridine, 5-iododeoxyuridine, and phosphonoacetic acid against herpes simplex virus types 1 and 2

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