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1.  Effects of (E)-5-(2-bromovinyl)-2'-deoxyuridine on proliferation of human fibroblasts, peripheral blood mononuclear cells, and granulocyte-monocyte progenitor cells in vitro. 
Inhibition of human fibroblasts, granulocyte-monocyte progenitor cells, and lymphocytes was observed at (E)-5-(2-bromovinyl)-2'-deoxyuridine concentrations ranging from 21 to 197 micrograms/ml. These concentrations were 10- to 100-fold above usual serum concentrations after oral administration. (E)-5-(2-Bromovinyl)-2'-deoxyuridine compares favorably with currently used antivirals in terms of in vitro myelotoxicity and immunotoxicity.
PMCID: PMC185945  PMID: 6660853
2.  In vitro susceptibility of varicella-zoster virus to E-5-(2-bromovinyl)-2'-deoxyuridine and related compounds. 
The in vitro susceptibility of eight strains of varicella-zoster virus (VZV) to E-5-(2-bromovinyl)-2'-deoxyuridine (BVDU) was examined in human embryonic fibroblasts by the following techniques: inhibition of focus formation by either cell-free VZV (4-day assay) or cell-associated VZV (2-day assay), inhibition of viral antigen formation (2-day assay), and inhibition of viral cytopathogenicity (15-day assay). The 50% inhibitory dose (ID50) of BVDU ranged from 0.001 microgram/ml (2-day assay) to 0.01 microgram/ml (15-day assay). BVDU appeared highly selective in its anti-VZV activity since even at concentrations as high as 100 micrograms/ml, BVDU did not markedly affect the viability of the host cells. The ID50 of BVDU for VZV was comparable to that of IVDU (E-5-(2-iodovinyl)-2'-deoxyuridine). Both drugs inhibited the replication of VZV at a much lower concentration than did other antiviral compounds such as iododeoxyuridine, ethyldeoxyuridine, arabinosylcytosine, arabinosyladenine, phosphonoacetic acid, iododeoxycytidine, and acycloguanosine. BVDU and IVDU were virtually inactive against a thymidine kinase-deficient VZV mutant, suggesting that phosphorylation by the viral enzyme is responsible, at least in part, for the selective anti-VZV activity of the compounds.
PMCID: PMC181824  PMID: 6282207
3.  Susceptibility of bovid herpesvirus 1 to antiviral drugs: in vitro versus in vivo efficacy of (E)-5-(2-Bromovinyl)-2'-deoxyuridine. 
The relative efficacies of a variety of antiviral drugs against bovid herpesvirus 1 was investigated. (E)-5-(2-Bromovinyl)-2'-deoxyuridine and trifluorothymidine were found to be inhibitory at doses of 0.01 micrograms/ml in in vitro yield reduction and plaque reduction assays. In contrast, acylovir was inactive even at concentrations as high as 1,000 micrograms/ml. Other drugs, including phosphonoformic acid, 9-beta-D-arabinofuranosyladenine, 5-iodo-2-deoxyuridine, and 1-beta-D-arabinofuranosylcytosine were active at concentrations previously shown to inhibit herpes simplex virus. Oral administration of (E)-5-(2-bromovinyl)-2'-deoxyuridine to calves infected with bovid herpesvirus 1 had no effect on the level of virus shedding, clinical signs, or susceptibility to secondary bacterial infection with Pasteurella haemolytica. The reason for this lack of in vivo activity was that sufficient levels of the drug in blood were not achieved by oral administration.
PMCID: PMC184794  PMID: 6307134
4.  Synergistic inhibition of human immunodeficiency virus type 1 replication by 5-ethyl-1-ethoxymethyl-6-(phenylthio)uracil (E-EPU) and azidothymidine in vitro. 
A novel 6-substituted acyclouridine derivative, 5-ethyl-1-ethoxymethyl-6-(phenylthio)uracil (E-EPU), has recently proved to be a highly potent and selective inhibitor of human immunodeficiency virus type 1 (HIV-1) in vitro. Combinations of 3'-azido-2',3'-dideoxythymidine (AZT) and E-EPU synergistically inhibit the replication of HIV-1 in MT-4 cells, whereas the cytotoxic effects of AZT and E-EPU on mock-infected MT-4 cells are not enhanced by the drug combination. Synergistic inhibition of HIV-1 replication has also been observed in peripheral blood lymphocytes. These results indicate that the combination of AZT and E-EPU should be further pursued in the treatment of AIDS.
PMCID: PMC245184  PMID: 1929304
5.  In vitro and in vivo inhibition of ortho- and paramyxovirus infections by a new class of sulfonic acid polymers interacting with virus-cell binding and/or fusion. 
A series of sulfonic acid polymers were shown to be potent and selective inhibitors of respiratory syncytial virus (RSV) and influenza A virus. The compounds inhibit the replication of RSV and influenza A virus in HeLa and MDCK cells, at concentrations of 0.16 and 4.0 micrograms/ml, respectively, and are nontoxic to growing cells at concentrations of > 100 micrograms/ml. The mode of antiviral action of the sulfonic acid polymers can be ascribed to inhibition of virus-cell fusion (for influenza A virus) or inhibition of both virus-cell binding and fusion (for RSV). The sulfonic acid prototype PAMPS [poly(2-acrylamido-2-methyl-1-propanesulfonic acid)], when administered intranasally to mice as a single dose of 10 or 50 mg per kg of body weight at the time of infection, completely inhibited influenza A virus replication (in lungs) and virus-associated lung consolidation in immunocompetent mice and completely protected NMRI and SCID (severe combined immune deficiency) mice against influenza A virus-associated mortality. When administered 1 h before or after virus inoculation, no protective effect was observed at a dose of 10 or 100 mg/kg. Sulfonic acid polymers exert selective inhibitory effects on RSV and influenza A virus replication.
PMCID: PMC284437  PMID: 8192454
6.  Inhibitory effects of selected antiviral compounds on human hepatitis B virus DNA synthesis. 
By using an assay system based on a human hepatoblastoma cell line (HB611) that continuously synthesizes hepatitis B virus DNA, the following compounds were found to inhibit hepatitis B virus DNA synthesis at concentrations that were significantly lower than their minimum cytotoxic concentrations: 9-(2-phosphonylmethoxyethyl)-2,6-diaminopurine (PMEDAP), (S)-9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine, 9-(phosphonylmethoxyethyl)adenine, 2',3'-dideoxy-2',3'-didehydrocytidine, and 2',3'-dideoxycytidine. The most potent compound was PMEDAP (50% effective concentration, 0.02 micrograms/ml). The selective index, or ratio of the 50% cytotoxic concentration to 50% effective concentration, of PMEDAP was greater than 750.
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PMCID: PMC245016  PMID: 2024975
7.  Ribavirin antagonizes inhibitory effects of pyrimidine 2',3'-dideoxynucleosides but enhances inhibitory effects of purine 2',3'-dideoxynucleosides on replication of human immunodeficiency virus in vitro. 
Antimicrobial Agents and Chemotherapy  1987;31(10):1613-1617.
The combined antiviral effects of various 2',3'-dideoxynucleosides and ribavirin on the replication of human immunodeficiency virus type 1 in MT-4 cells have been examined. Ribavirin antagonized the antiviral activity of the pyrimidine 2',3'-dideoxynucleosides (3'-azido-2',3'-dideoxythymidine, 2',3'-dideoxythymidin-2'-ene, 2',3'-dideoxycytidine, and 2',3'-dideoxycytidin-2'-ene), but enhanced the antiviral activity of the purine 2',3'-dideoxynucleosides (2',3'-dideoxyadenosine and 2',3'-dideoxyguanosine). Combinations of the 2',3'-dideoxynucleosides with each other were also examined. These combinations resulted in an additive to subsynergistic effect.
PMCID: PMC175001  PMID: 3435108
8.  Prolonged herpes simplex virus latency in vitro after treatment of infected cells with acyclovir and human leukocyte interferon. 
We previously demonstrated that herpes simplex virus type 1 (HSV-1) can be established in a latent form in vitro by the treatment of HSV-infected human cells with (E)-5-(2-bromovinyl)-2'-deoxyuridine (BVDU) in combination with human leukocyte interferon (IFN-alpha). We now report that the substitution of BVDU with 9-[(2-hydoxyethoxy)methyl]guanine (acyclovir; ACV) during a combined treatment with IFN-alpha inhibited HSV-1 replication and established in vitro virus latency that could be maintained for a longer period after inhibitor removal and a continued incubation at 37 degrees C. By contrast, the treatment of HSV-1-infected cells with combined IFN-alpha and 9-(1,3-dihydroxy-2-propoxymethyl)guanine, a congener of ACV, failed to establish in vitro virus latency. Furthermore, none of these inhibitors used alone was sufficient to establish in vitro virus latency. The use of nucleoside analogs differing from BVDU in their modes of action has enabled us to initiate studies designed to extend in vitro virus latency.
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PMCID: PMC180447  PMID: 3010847
9.  (E)-5-(2-bromovinyl)-2'-Deoxyuridine in the treatment of experimental herpes simplex keratitis. 
IDU (5-iodo-2'-deoxyuridine), BVDU [(E)-5-(2-bromovinyl)-2'-deoxyuridine] and placebo ointments were studied for their effects on experimental herpes simplex (type 1) keratoconjuncitivitis in rabbits. When treatment was begun 65 h after virus inoculation, both BVDU and IDU prevented development of keratitis. Both BVDU and IDU were also effective in suppressing the severity of conjunctivitis, and in this respect, BVDU proved significantly better than IDU. When treatment was started 110 h after virus inoculation, BVDU proved significantly better than IDU in promoting healing of established keratitis.
PMCID: PMC283717  PMID: 7352751
10.  Antirhinovirus activity of purine nucleoside analogs. 
A wide variety of purine nucleoside (mainly tubercidin and adenosine) analogs, which had previously been shown to inhibit the replication of a broad spectrum of RNA viruses, were evaluated for their antirhinovirus activity in human diploid (WI-38) fibroblasts. Tubercidin, 5-(1-hydroxyethyl)tubercidin, 5-(2-buten-1-yl)tubercidin, toyocamycin, and sangivamycin emerged as the most potent inhibitors. These compounds inhibited the replication of rhinovirus types 1A, 1B, and 9 at an MIC well below 1 microgram/ml. However, these compounds proved cytotoxic for the uninfected host cells at concentrations which were only slightly higher (3- to 10-fold, on the average) than those required for inhibition of rhinovirus replication. The most selective inhibitor of rhinovirus replication was 3-deazaguanine, with a selectivity index of 50. None of the carbocyclic and acyclic analogs of adenosine tested exhibited a potent or selective antirhinovirus activity.
PMCID: PMC180418  PMID: 3013084
11.  5-Propyl-2'-deoxyuridine: a specific anti-herpes agent. 
In both primary rabbit kidney cells and human skin fibroblasts, 5-propyl-2'-deoxyuridine proved inhibitory to herpes simplex virus at a concentration as low as 1 micrograms/ml, whereas concentrations higher than 200 micrograms/ml were required to inhibit vaccinia virus replication or normal cell metabolism.
PMCID: PMC352280  PMID: 233730
12.  Inhibitory effects of acyclic nucleoside phosphonate analogs, including (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine, on Epstein-Barr virus replication. 
Antimicrobial Agents and Chemotherapy  1991;35(11):2440-2443.
(S)-9-(3-Hydroxy-2-phosphonylmethoxypropyl)adenine [(S)-HPMPA], (S)-9-(3-hydroxy-2-phosphonylmethoxypropyl)-2,6-diaminopurine [(S)-HPMPDAP], cyclic (S)-HPMPA [(S)-cHPMPA], 9-(2-phosphonylmethoxyethoxyethyl)-2,6-diaminopurine (PMEDAP), and (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine [(S)-HPMPC] were examined for their inhibitory effects on Epstein-Barr virus (EBV) replication. The 50% effective concentrations for inhibition of viral DNA replication were 0.16, 0.03, 2.0, 1.5, and 0.08 microM for PMEDAP, (S)-HPMPC, (S)-HPMPDAP, (S)-cHPMPA, and (S)-HPMPA, respectively. The relative efficacies based on the in vitro therapeutic index was (S)-HPMPC (5,000) greater than PMEDAP (1,000) = (S)-HPMPA (1,000) greater than (S)-cHPMPA (136) greater than (S)-HPMPDAP (78). Certain ratios of combinations of (S)-HPMPC with 3'-azido-3'-deoxythymidine produced a synergistic inhibitory effect on EBV genome replication, but others exhibited an antagonistic effect. These results indicate that this series of acyclic nucleoside phosphonate analogs, and in particular (S)-HPMPC, are potent and selective anti-EBV agents in vitro.
PMCID: PMC245402  PMID: 1666500
13.  Metabolic fate of (E)-5-(2-bromovinyl)-2'-deoxyuridine in herpes simplex virus- and mock-infected cells. 
(E)-5-(2-Bromovinyl)-2'-deoxyuridine is a potent antiherpes compound with far better activity against herpes simplex virus type 1 than type 2. To understand the role of drug metabolism in this differential antiviral activity, we examined the metabolic fate of this drug in virus-infected and mock-infected Vero cells by high-pressure liquid chromatography. After 8 h of incubation in which cells were exposed to 10 micrograms of the drug per ml, 63 pmol/10(6) cells of the parent compound was detected in acid-soluble extracts of mock-infected cells. Herpes simplex virus-infected cells, however, incorporated or metabolized, or both, up to 11,310 pmol/10(6) cells. Type 1-infected cells metabolized the drug to the triphosphate where as many as 5,565 pmol/10(6) cells were detected. In contrast, three strains of type 2-infected cells metabolized the drug to the monophosphorylated nucleotide and no further. The amount of drug getting into the cells was virus strain and inoculum dependent. These studies indicate that poor substrate acceptance of (E)-5-(2-bromovinyl)-2'-deoxyuridine monophosphate by herpes simplex virus type 2-specified thymidylate kinase is an important factor in situ in infected cells, preventing anabolism of the parent compound to its active triphosphorylated form. This may account for its type specificity.
PMCID: PMC180009  PMID: 6097176
14.  Effect of (E)-5-(2-bromovinyl)-2'-deoxyuridine on synthesis of herpes simplex virus type 1-specific polypeptides. 
The antiherpesvirus agent (E)-5-(2-bromovinyl)-2'-deoxyuridine caused marked alterations in the synthesis and processing of several herpes simplex virus type 1 (HSV-1)-infected-cell polypeptides. Analogous to other thymidine analogs, there was a dose-dependent decrease in several beta and gamma polypeptides and an accumulation of HSV-1 thymidine kinase. In contrast to the action of other thymidine analogs, there were alterations in alpha polypeptides, including an increase in the synthesis and phosphorylation of infected-cell polypeptide 4b and a decrease in the synthesis of infected-cell polypeptide 27. The phosphorylation of several other HSV-1 phosphoproteins was mildly inhibited. (E)-5-(2-Bromovinyl)-2'-deoxyuridine inhibited the glycosylation of the major HSV-1 glycoproteins, and this activity appeared to be independent of the incorporation of the drug into the viral DNA. Thus, the alterations in HSV-1 polypeptide expression appear to be due to the presence of the drug in a low-molecular-weight form as well as its presence in the viral DNA. This suggests that this analog or a phosphorylated derivative might act as an inhibitor of an enzyme(s) responsible for posttranslational modification of polypeptides.
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PMCID: PMC185587  PMID: 6329089
15.  Synergistic antiviral effects of antiherpes compounds and human leukocyte interferon on varicella-zoster virus in vitro. 
The four antiherpes compounds acyclovir, adenine arabinoside, bromovinyldeoxyuridine, and phosphonoformic acid showed an additive to synergistic effect with human leukocyte interferon in inhibiting focus formation by three different strains of varicella-zoster virus in human embryonic fibroblasts.
PMCID: PMC185568  PMID: 6329083
16.  Oral antiviral drugs in experimental herpes simplex keratitis. 
Chronic oral administration of acyclovir or bromovinyl deoxyuridine to rabbits did not prevent recurrence of virus shedding or clinical corneal disease, nor did it alter the clinical course of recurrences of ocular herpetic disease or result in the appearance of resistant virus in tears.
PMCID: PMC185402  PMID: 6318664
17.  Relative potencies of different anti-herpes agents in the topical treatment of cutaneous herpes simplex virus infection of athymic nude mice. 
Thirteen established anti-herpes compounds have been directly compared in a single assay system for their effects on the development of herpetic skin lesions, and mortality associated therewith, in athymic nude (nu/nu) mice inoculated intracutaneously with herpes simplex virus type 1 (KOS). When applied topically (at 1% in a water-soluble ointment), phosphonoacetic acid, E-5-(2-bromovinyl)-2'-deoxyuridine, acycloguanosine, and trisodium phosphonoformate emerged as the most active agents.
PMCID: PMC352929  PMID: 526011
18.  Efficacy of (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine in various models of herpes simplex virus infection in mice. 
The phosphonylmethoxyalkyl derivative (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine (HPMPC) was evaluated for its in vivo efficacy in several model infections for herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) and thymidine kinase-deficient (TK-) HSV-1 in mice. In hairless mice infected intracutaneously with HSV-1 or HSV-2, HPMPC completely suppressed all manifestations of the disease (skin lesions, paralysis of the hind legs, and mortality) if it was administered topically at a concentration of as low as 0.1, 0.3, or 1%. Similarly, HPMPC completely suppressed TK- HSV-1 infection in athymic nude mice if it was administered topically at 0.1 or 0.3% or intraperitoneally at 100 or 250 mg/kg/day. HPMPC was also effective against intraperitoneal HSV infection if it was given orally at a dose of 50 mg/kg/day or higher. In mice inoculated intracerebrally with HSV-2, intraperitoneal HPMPC treatment achieved a significant and dose-dependent protection at doses ranging from 5 to 400 mg/kg/day. The protective effect of HPMPC (at 200 mg/kg/day) was accompanied by a complete inhibition of virus multiplication in the brain. In all models of infections studied, the efficacy of HPMPC proved to be superior to that of acyclovir. The most remarkable feature of HPMPC was that a single administration of the compound, even as late as 4 days after infection, conferred significant protection against HSV-1 or HSV-2 infection. Topical or systemic HPMPC treatment is efficacious in murine models of HSV-1, HSV-2, and TK- HSV infections.
PMCID: PMC245082  PMID: 2069375
19.  Novel sulfated polymers as highly potent and selective inhibitors of human immunodeficiency virus replication and giant cell formation. 
Novel synthetic sulfated polymers, namely, sulfated polyvinyl alcohol (PVAS) and sulfated copolymers of acrylic acid with vinyl alcohol (PAVAS), proved to be potent and selective inhibitors of human immunodeficiency virus type 1 (HIV-1) and HIV-2 in vitro. The compounds completely inhibited HIV-1-induced cytopathogenicity in MT-4 cells and HIV-1 antigen expression in CEM cells at a concentration of 0.8 micrograms/ml. They were equally effective against HIV-2 replication. In addition, and in contrast to azidothymidine, PAVAS and PVAS suppressed HIV-1-induced giant cell (syncytium) formation, a process that may account for the depletion of T4 lymphocytes in patients with acquired immunodeficiency syndrome. PAVAS and PVAS completely blocked giant cell formation at a concentration of 4 micrograms/ml, whereas for dextran sulfate a concentration of 100 micrograms/ml was required to achieve complete inhibition of giant cell formation. As has been demonstrated previously for the sulfated polysaccharides, the mechanism of action of PAVAS and PVAS resides in the inhibition of virus adsorption to the cells.
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PMCID: PMC171534  PMID: 2327749
20.  9-(2-Phosphonylmethoxyethyl)adenine in the treatment of murine acquired immunodeficiency disease and opportunistic herpes simplex virus infections. 
Antimicrobial Agents and Chemotherapy  1989;33(11):1864-1868.
The murine model of acquired immunodeficiency disease was used to evaluate both the antiretroviral and antiherpetic activities of the acyclic nucleotide analog 9-(2-phosphonylmethoxyethyl)adenine (PMEA). The antiretroviral activity of PMEA was compared with that of azidothymidine (AZT) in mice receiving the drug either immediately after infection or at late times in disease progression. Both AZT (oral, 30 mg/kg) and PMEA (parenteral, 25 and 5 mg/kg) were effective in slowing the development of disease when administered daily beginning on the day of infection. In contrast, neither drug alone was effective in modifying disease outcome when administered several weeks after viral infection. Human recombinant alpha interferon (rhuIFN alpha-B/D at 5 x 10(7) U/kg) was also ineffective when administered late in the course of disease. However, when administered in combination, both alpha interferon and PMEA (25 mg/kg) were able to suppress disease progression even when treatment was initiated as late as 3 weeks postinfection. Mice that were immunocompromised due to LP-BM5 virus infection were highly susceptible to acute (lethal) infection with herpes simplex virus type 1, whereas their immunocompetent littermates were not. PMEA was as effective as acyclovir in the treatment of opportunistic herpes simplex virus type 1 infections in LP-BM5 virus-infected mice. Thus, like AZT, PMEA was effective against retrovirus infection, and, like acyclovir, PMEA was effective against herpes simplex virus type 1 infection. This gives PMEA the unique potential of being useful in the treatment of opportunistic herpes simplex virus infections as well as the underlying retroviral disease.
PMCID: PMC172778  PMID: 2482011
21.  Efficacy of phosphonylmethoxyalkyl derivatives of adenine in experimental herpes simplex virus and vaccinia virus infections in vivo. 
The phosphonylmethoxyalkyl derivatives (S)-9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine [(S)-HPMPA], 9-(2-phosphonylmethoxyethyl)adenine (PMEA), and 9-(2-phosphonylmethoxyethyl)-2,6-diaminopurine (PMEDAP) were evaluated for their in vivo efficacies in several animal model infections, i.e., mice infected intravenously with vaccinia virus and mice infected intracutaneously, intraperitoneally, or intracerebrally with herpes simplex virus type 1 (HSV-1) or type 2 (HSV-2) or thymidine kinase-deficient (TK-) HSV-1. (S)-HPMPA inhibited the development of tail lesions caused by vaccinia virus if it was administered intraperitoneally or subcutaneously at a dosage as low as 5 mg/kg per day. All three compounds completely suppressed the development of skin lesions and the mortality associated therewith in hairless or athymic nude mice inoculated intracutaneously with HSV-1 or TK- HSV-1, if they were administered topically at a concentration as low as 0.1%; when (S)-HPMPA was applied topically at a concentration of greater than or equal to 0.3%, it completely abrogated mortality resulting from intracutaneous HSV-2 infection. Most dramatic were the effects shown by the compounds in mice inoculated intracerebrally with HSV-1, HSV-2, or TK- HSV-1, in which all three compounds given intraperitoneally at a dose of 50 or 100 mg/kg per day effected a significant reduction in the mortality rate of HSV-1-infected mice. The mortality of mice infected intracerebrally with HSV-2 or TK- HSV-1 was significantly reduced even when (S)-HPMPA was given at doses as low as 10 mg/kg per day. These data point to the great potential of the phosphonylmethoxyalkylpurines for both topical and parenteral treatment of HSV-1, HSV-2, and TK- HSV-1 infections.
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PMCID: PMC171454  PMID: 2719463
22.  (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine, a potent and selective inhibitor of human cytomegalovirus replication. 
Antimicrobial Agents and Chemotherapy  1988;32(12):1839-1844.
From a series of phosphonylmethoxyalkylpurine and -pyrimidine derivatives, (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine [(S)-HPMPC] emerged as a particularly potent and selective inhibitor of the replication of human cytomegalovirus (CMV). Its potency against CMV was similar to that of the structurally related adenine derivative (S)-HPMPA but higher than that of the reference compounds phosphonoformate and 9-(1,3-dihydroxy-2-propoxymethyl)guanine (DHPG). The minimum concentrations of phosphonoformate, DHPG, (S)-HPMPA, and (S)-HPMPC required to inhibit CMV plaque formation by 50% were 15, 0.7, 0.1, and 0.07 microgram/ml, respectively. The selectivity indices of phosphonoformate, DHPG, (S)-HPMPA, and (S)-HPMPC, as determined by the ratio of the 50% inhibitory concentration for cell growth to the 50% inhibitory concentration for plaque formation for CMV (AD-169 strain), were 14, 150, 200 and 1,500, respectively. Corresponding values for the CMV Davis strain were 20, 200, 100, and 1,000, respectively. (S)-HPMPC was inhibitory to CMV plaque formation even when added to the cells at 24 or 48 h postinfection. When (S)-HPMPC was added immediately postinfection, a 24- or 48-h incubation time sufficed to obtain a marked inhibitory effect on CMV replication. Such limited incubation time was insufficient for DHPG to achieve any protection against CMV.
PMCID: PMC176029  PMID: 2854454
23.  Selective inhibitory effect of (S)-9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine and 2'-nor-cyclic GMP on adenovirus replication in vitro. 
The inhibitory effects of 20 selected antiviral compounds on the replication of adenoviruses (types 1 to 8) in vitro were investigated. While 18 compounds were ineffective, 2 compounds, namely (S)-9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine [(S)-HPMPA] and 9-[(2-hydroxy-1,3,2-dioxaphosphorinan-5-yl)oxymethyl]guanine P-oxide (2'-nor-cyclic GMP), were highly effective against all adenovirus types assayed in human embryonic fibroblast cultures. Their 50% inhibitory doses were 1.1 microgram/ml for (S)-HPMPA and 4.1 micrograms/ml for 2'-nor-cyclic GMP. They were nontoxic for the host cells at the effective antiviral doses.
PMCID: PMC174721  PMID: 3566256
24.  Comparative efficacy of antiherpes drugs in different cell lines. 
A selection of antiherpes compounds including bromovinyldeoxyuridine (BVDU), acyclovir (ACV), and fluoroiodoaracytosine (FIAC) were compared for their inhibitory effects on herpes simplex virus type 1 (strain KOS) replication in a wide variety of human, simian, feline, and murine cell lines. The 50% inhibitory doses of the compounds varied considerably from one cell line to another, i.e., from 0.01 to 2 micrograms/ml for ACV and from 0.004 to 0.2 micrograms/ml for BVDU and FIAC. However, the relative order of antiviral potency remained constant, thus (in order of decreasing potency) BVDU greater than FIAC greater than ACV, for all cell lines studied except for the murine embryo cells, in which the order of decreasing potency was BVDU greater than ACV greater than FIAC, and for the feline lung cells, in which the order of decreasing potency was FIAC greater than ACV greater than BVDU.
PMCID: PMC181961  PMID: 6282214
25.  Antifungal and antibacterial activities of diarylamidine derivatives. 
The antifungal and antibacterial properties of a series of 70 diarylamidine derivatives were evaluated. Several of these compounds exhibited considerable antimicrobial potency. A survey of the structure-activity relationship demonstrated that minor structural variations resulted in significant changes of antimicrobial activity. In general, the structural features required for antifungal activity coincided with those required for antibacterial activity. Both the antifungal and the antibacterial properties of the diarylamidines depended on the presence and the positions, of both amidino groups, on the nature of the central bridge connecting the two aryl moieties, and on the nature of these aryl residues (preferably indole). The most active compound was evaluated for its activity against Candida albicans infection in mice.
PMCID: PMC283976  PMID: 7447403

Results 1-25 (56)