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Biomedical subjects

V S Gupta

Publications and source records attributed to V S Gupta.

At least 55 records · Page 3Linked to original sources
PubMed1983

Comparison of the antiviral effects of 5-methoxymethyldeoxyuridine-5'-monophosphate with adenine arabinoside-5'-monophosphate.

Methoxymethyldeoxyuridine-5'-monophosphate (MMUdR-MP) and arabinofuranosyladenine-5'-monophosphate (Ara-AMP) had significant antiviral activity against herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) in RK-13 and Vero cells. MMUdR-MP and Ara-AMP were more potent than methoxymethyldeoxyuridine (MMUdR) and arabinofuranosyladenine (Ara-A) against the MS strain of HSV-2. MMUdR-MP inhibited replication of HSV-1r (mutant resistant to MMUdR). MMUdR in combination with Ara-AMP showed additive activity; whereas the MMUdR-MP and Ara-AMP combination was antagonistic against herpes viruses. MMUdR in combination with Ara-A was synergistic in reducing the log virus yield. Cytotoxicity (microscopic lesions) was observed on exposure to MMUdR-MP and Ara-AMP at 450 and 90 microM, respectively. Rapidly proliferating RK-13 cells exposed to Ara-AMP (64 microM) were killed. In the same system, the cells surviving after incubation with MMUdR-MP (650 microM), multiplied at an almost normal rate.

Animals↗
PubMed1981

Pharmacological studies on 5-methoxymethyl-2'-deoxyuridine: a new antiviral agent.

Pharmacokinetic and pharmacodynamic properties of 5-methoxymethyl-2'-deoxyuridine (MMUdR), a drug with potent antiviral activity against herpes simplex virus, were investigated. After i.v. administration of [2-14C]MMUdR at 50 and 25 mg/kg to rats, the overall half life of the drug (T 1/2 Kel) was calculated to be 32 to 35 min. The biological half life of the drug (T 1/2 beta) was 89 min and the distribution half life (T1/2 alpha) was 6 min. The specific volume of distribution was calculated to be 1.28 to 1.35 liters/kg and the total body clearance rate of the drug was 10 ml/min/kg. The data were analyzed on the basis of a two-compartment open pharmacokinetic model. After i.p. administration of 50 mg/kg of [2-14C]MMUdR to mice, peak plasma levels of 35.6 micrograms/ml were attained in 10 min. The highest tissue concentrations of [2-14C]MMUdR in mice were 63 micrograms/g in kidneys (30 min) followed by 36 micrograms/g in liver and spleen and 30 to 32 micrograms/g in lungs and gut (20 min). MMUdR did not undergo biotransformation in plasma but urine was found to contain MMUdR (greater than 80%) and a small amount of radioactivity which comigrated with MMUdR monophosphate. Administration of 500 mg/kg of MMUdR i.v. to New Zealand White rabbits did not produce any observable effects on the heart rate, ECG pattern or respiration rate. Vasodilation of 39-sec duration was observed immediately after administration of MMUdR.

Animals↗
PubMed1980

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

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%.

Animals↗
PubMed1980

Procion dyes as affinity ligands and reporter groups for dihydrofolate reductase from Walker 256 carcinoma.

Procion dye - agarose matrices were investigated for isolation of dihydrofolate reductase (FAH2R) from Walker 256 carcinosarcoma. Cibacron blue F3GA, Procion blue MX4GD, Procion blue HERD, and Procion red H3BN covalently bound to agarose adsorbed greater than 85% of pure FAH2R from 100 mM imidazole buffer, pH 6.3, and this enzyme was specifically and quantitatively eluted with 1 mM folate. The capacity and selectivity of the dye-agarose matrices were greater at low dye incorporation. Difference spectroscopy of the FAH2R - Cibacron blue F3GA complex indicated that 2 mol of the dye were bound in hydrophobic environments with each mole of the enzyme. NADPH and folate (at twofold molar excess over enzyme) or 1 M KCl displaced only 1 mol of Cibacron blue F3GA. This dye interacted stoichiometrically in a specific manner with the active site of FAH2R probably spanning the folate and NADP binding sites. The second dye molecule appears to be bound in a nonspecific hydrophobic manner. Selected Procion dye - agarose matrices can be used for partial purification of FAH2R from tumor homogenate.

Animals↗
PubMed1980

Comparative efficacy of 5-methoxymethyl-2'-deoxyuridine, 9 beta-D-arabinofuranosyladenine and 5-iodo-2'-deoxyuridine in the treatment of experimental herpes simplex keratitis.

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 effective as 5% Ara-A or 0.1% IUdR in controlling the viral keratitis.

Animals↗
PubMed1979

Evaluation of 1-(3,4-dichlorophenyl)-4-dimethylaminomethyl-1-nonen-3-one hydrochloride effect on nucleic acid and protein syntheses using murine leukemia L-1210 cells.

Several Mannich bases derived from conjugated styryl ketones were shown to have potent cytotoxicity toward murine leukemia L-1210 cells and Walker 256 carcinosarcoma cells in culture. The most cytotoxic derivative, (E)-1-(3,4-dichlorophenyl)-4-dimethylaminomethyl-1-nonen-3-one hydrochloride, profoundly inhibited the incorporation of tritiated leucine into protein(s) and tritiated deoxythymidine into DNA at concentrations of 0.79-1.32 muM in L-1210 cells. At higher concentrations, incorporation of triated uridine into RNA and tritiated deoxyuridine into DNA was inhibited to a lesser degree. This compound failed to inhibit the enzymes thymidylate synthetase or dihydrofolate reductase up to a concentration of 10-4 M and was ineffective in retarding the growth of the Walker 256 carcinosarcoma in rats.

Amines↗
PubMed1977

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

5-Methoxymethyl-2'-deoxyuridine (MMUdR), a drug with potent antiviral activity in vitro against Herpes simplex virus, was investigated for its immunosuppressive effects. Doses as high as 2000mg/kg given daily for 9 days were not immunosupporessive as judged by the fact that treated animals produced normal immune responses to sheep erythrocytes, Brucella bacteria, and Herpes simplex virus.

Animals↗
PubMed1977

Schedule-dependent antitumor effects of methotrexate and 5-fluorouracil.

The antitumor effects of methotrexate with 5-fluorouracil against the Sarcoma 180 mouse tumor model were found to be schedule dependent. Pretreatment of tumor-bearing animals with methotrexate significantly enhanced the antitumor activity of the combination relative to simultaneous treatment or to those with methotrexate following 5-fluorouracil. These studies indirectly support the hypothesis that methotrexate pretreatment with 5-fluorouracil is synergistic by increasing the amount of thymidylate synthetase bound to the active metabolite of 5-fluorouracil.

Animals↗
PubMed1975

Synthesis and cell culture studies on the antiviral activity of 5-mercaptomethyl-2'-deoxyuridine.

Treatment of 5-mercaptomethyluracil (I) with trimethylsilyl chloride in the presence of triethylamine gave 2,4,5-tris-(trimethylsilyl)-5-mercaptomethyluracil (II) which, upon coupling with 2-deoxy-3,5-di-O-(p-toluoyl)-D-erythro-pentofuranosyl chloride, furnished as anomeric mixture of fully substituted 2'-deoxy ribonucleosides. The nucleoside with beta configuration (III) was predominantly formed and was isolated as a crystalline solid. The free nucleoside IV was obtained by removal of blocking groups by sodium methoxide catalyzed deacylation, deionization under reducing atmosphere, and chromatography on neutral alumina. IV is oxidized to the corresponding disulfide V in solution in the absence of thiols. IV was found to be markedly inhibitory against the herpes virus of infectious bovine rhinotracheitis (IBR). Against this virus, IV was found to be as potent as 5-iododeoxyuridine and cytosine arabinoside when added 18 hr before virus infection.

Animals↗
PubMed1975

Comparison of the antiviral effects of 5-methoxymethyl-deoxyuridine with 5-iododeoxyuridine, cytosine arabinoside, and adenine arabinoside.

The antiviral activity of 5-methoxymethyl-2'-deoxyuridine (MMUdR) was compared with that of 5-iodo-2'-deoxyuridine (IUdR), cytosine arabinoside (Ara-C), and adenine arabinoside (Ara-A). At concentrations of 2 to 4 mug/ml, MMUdR was inhibitory to herpes simplex virus type 1, but concentrations as high as 128 mug/ml were not inhibitory to three other herpesviruses tested (equine rhinopneumonitis virus, murine cytomegalovirus, and feline rhinopneumonitis virus) or to vaccinia virus. The other nucleosides, in contrast, were inhibitory at similar concentrations (1 to 8 mug/ml) against all viruses tested. The inhibition of HSV-1 by MMUdR appeared to be the result of interference with virus replication rather than the result of drug toxicity to host cells. The drug was not toxic to host cells at 100 times the antiviral concentrations, and pretreatment of host cells with high concentrations of MMUdR had no effect on subsequent virus replication. Combination of MMUdR with either IUdR, Ara-A, or Ara-C gave an enhanced antiviral effect, suggesting that the mechanism of action of MMUdR is different from that of the other three drugs. Antiviral indexes were calculated for each compound and were found to be >250, 80, 40, and 8 for MMUdR, IUdR, Ara-A, and Ara-C, respectively. These were defined as the minimum dose at which toxicity was observed microscopically divided by the dose which reduced plaque numbers by 50%.

Animals↗
PubMed1975

A pharmacological study of chloramphenicol in horses.

Pharmacological disposition of chloramphenicol was studied in horses. Minimum levels of the antibiotic (greater than or equal to 5 mu g/ml) in blood or plasma recommended to combat infections could not be achieved by 4.4 and 8.8 mg/kg I.V. or 30 and 50 mg/kg I.M. or 30 mg/kg oral (as palmitate salt) doses of chloramphenicol. Increasing the dose to 19.8 and 26.4 mg/kg I.V. provided such levels for about two and three hours respectively. A combination of 20 mg/kg I.V. and 30 mg/kg I.M. administered simultaneously did not provide more prolonged levels than 26.4 mg/kg I.V. alone. Chloramphenicol succinate produced higher but not more prolonged levels in blood and plasma than those produced by pure chloramphenicol. Succinate salt is very little, if at all, bound to red blood corpuscles. Plasma half life and the apparent volume of distribution of chloramphenicol in horses were determined as 0.98 hours and 0.92 L/kg, respectively. At 5-10 mu g/ml concentrations in equine plasma approximately 30 percent of the chloramphenicol is bound to plasma proteins. From these studies it is concluded that the biological half life of chloramphenicol may be too short for therapeutic application against systemic infections in horses.

Administration, Oral↗
PubMed1974

Cell culture studies on the antiviral activity of ether derivatives of 5-hydroxymethyldeoxyuridine.

The antiviral activity of several ether derivatives of 5-hydroxymethyldeoxyuridine against the herpesvirus of infectious bovine rhinotracheitis was determined in monolayer cultures of secondary bovine fetal kidney cells. 5-Methoxy-methyldeoxyuridine (OCH(3)UdR) was found to be markedly inhibitory against this virus. Pretreatment of the cells with OCH(3)UdR, simultaneous addition of OCH(3)UdR with virus to the cells, and postinfection treatment with OCH(3)UdR were found to be effective in inhibiting virus-induced cytopathogenic effect. Against this virus, OCH(3)UdR was found to be as potent as 5-iododeoxyuridine and cytosine arabinoside. The alpha-anomer of OCH(3)UdR did not show antiviral activity. Preliminarly toxicity studies indicate that OCH(3)UdR has a very low acute toxicity.

Animals↗