Inhibition of Rhinovirus by Isatin Thiosemicarbazone Analogues

Gladych, J. M. Z.; Hunt, J. H.; Jack, Dominic; Haff, R. F.; Boyle, J. J.; Stewart, Richard C.; Ferlauto, R. J.

doi:10.1038/221286b0

Cited by 41 publications

(15 citation statements)

References 4 publications

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“…As uridine analogs, 3-deazauridine, 3'-C-methyluridine, and 5'-deoxy-5-fluorouridine were included in our study, and so were the ribavirin analogs T-25 and T-26. 3-Methylquercetine is active against poliovirus (27), and thiosemicarbazone is a well-known antipoxvirus agent (10). None of these compounds proved effective against RSV.…”

Section: Discussionmentioning

confidence: 99%

Inhibitory effects of antiviral compounds on respiratory syncytial virus replication in vitro

Kawana¹,

Shigeta²,

Suzuki³

et al. 1987

Antimicrob Agents Chemother

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We examined the inhibitory effect of 20 antiviral compounds, including ribavirin, on the replication of respiratory syncytial virus in HeLa and HEp-2 cell cultures. Of the compounds studied, pyrazofurin and 3-deazaguanine emerged as more potent inhibitors of respiratory syncytial virus than ribavirin. Based on their inhibitory effect on the cytopathogenicity of respiratory syncytial virus in HeLa cells, the average 50% effective dose of pyrazofurin and 3-deazaguanine for eight strains was 0.07 and 1.65 ,ug/ml, respectively; that of ribavirin was 5.82 p.g/ml. The cytotoxicity of these compounds for HeLa cells was examined by monitoring the incorporation of radiolabeled uridine into cellular RNA. The selectivity indexes of pyrazofurin and 3-deazaguanine exceeded that of ribavirin by 70-and 11-fold, respectively. Pyrazofurin, 3-deazaguanine, and ribavirin inhibited both viral antigen expression and syncytium formation in HeLa cell cultures, as assessed by an indirect immunofluorescence assay. In these assays, pyrazofurin and 3-deazaguanine again proved more potent than ribavirin. 2,5-Diamidinoindole and carbodine were less potent than ribavirin. Various other compounds, i.e., 3-adenin-9-yl-2-hydroxypropanoic acid isobutyl ester, 3-deazauridine, 3'-C-methyluridine, 5'-deoxy-5-fluorouridine, 5-cyanoimidazole-4-carboxamide, and its ribofuranosyl derivative, did not inhibit the cytopathic effect of the Long strain of respiratory syncytial virus at concentrations -125 pLg/ml. Tubercidin, 5-chlorotubercidin, xylotubercidin, neplanocin A, thiosemicarbazone R, and 3-methylquercetine were too toxic to HeLa cells for their inhibitory effects on respiratory syncytial virus to be examined.Respiratory syncytial virus (RSV) causes lower respiratory tract infections such as bronchiolitis and pneumonia in infancy and early childhood. Most clinicians consider RSV one of the most important agents of acute respiratory disease in children, and almost 50% of infants are expected to suffer from RSV infection during their first winter (15,16,20,32,35). Inactivated RSV vaccine does not protect against natural infection and leads to an unusual immune response and even lung inflammation during the course of a subsequent natural infection (21). Recent research efforts have therefore focused on the development of either potent live RSV vaccines or effective antiviral compounds.Following reports that ribavirin may reduce the severity of illness and amount of virus shed in acute respiratory infections due to RSV or influenza B virus (13,14,23,37), the drug has been approved in aerosol form for the chemotherapy of RSV infections. This has prompted the search for antiviral compounds that may be as effective, if not more effective, against RSV than ribavirin. We have now investigated the inhibitory effects of 20 antiviral compounds, including ribavirin, on the replication of RSV in vitro.MATERIALS AND METHODS Viruses. The Long, S-2, and S-8 strains of RSV were kindly provided by Y. Numazaki, National Sendai Hospital, Sendai, Japan. The 58-8, 58-7,...

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Section: Discussionmentioning

confidence: 99%

Inhibitory effects of antiviral compounds on respiratory syncytial virus replication in vitro

Kawana¹,

Shigeta²,

Suzuki³

et al. 1987

Antimicrob Agents Chemother

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“…The search for effective antirhinovirus agents has yielded a wealth of compounds belonging to widely varying chemical classes: thiosemicarbazones (20), isoquinolines (35,43), triazinoindoles (27), guanidines (5), benzoates (30), furanyls (2), benzimidazoles (12), thiourea (18), diketones (14,16,17), flavans (3,32), flavones (25), chalcones (24), nitrobenzenes (34,41), and isoxazoles (15,31). The most recently developed antirhinovirus compounds (3,15,24,31) reach their MICs within the range of 0.001 to 0.01 ,ug/ml.…”

mentioning

confidence: 99%

Antirhinovirus activity of purine nucleoside analogs

Clercq¹,

Bernaerts²,

Bergstrom³

et al. 1986

Antimicrob Agents Chemother

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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-(l-hydroxyethyl)tubercidin, 5-(2-buten-lyl)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 ,ug/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.The search for effective antirhinovirus agents has yielded a wealth of compounds belonging to widely varying chemical classes: thiosemicarbazones

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“…The maximum drug doses permitting normal WI-38 cell maintenance have been reported to be 159 /tg/ml for SK&F 21687, and 252 ,«g/ml for SK&F 30097 [5].…”

Section: Resultsmentioning

confidence: 99%

“…Antiviral com pounds for chemoprophylactic or therapeutic control of this infection have been sought. A group of 3-substituted triazinoindoles, analogues of isatin-/J-thiosemicarbazone, have been reported to exert broad spectrum antiviral activity in vitro [5,6] and are active against a large number of rhinovirus serotypes [7], One of these compounds showed a suggestive activity against experimental rhinovirus infection in chimpanzees [2].…”

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confidence: 99%

Failure of a 3-Substituted Triazinoindole in the Prevention of Experimental Human Rhinovirus Infection

Togo¹,

Schwartz²,

Hornick³

1973

Chemotherapy

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Abstract. Six rhinovirus serotypes showed in vitro susceptibility to two analogues (SK&F 21687 and SK&F 30097) of 3-substituted triazinoindole compounds. The intranasal SK&F 21687 medica tion did not prevent upper respiratory illness in 10 men who were challenged with rhinovirus type 44. No differences in the frequency and severity of clinical illness, virus shedding patterns, and serum and respiratory secretory antibody responses were detected between these drug-treated men and 10 placebo control subjects. The failure to affect the course of the illness may have been due to the insolubility of the test drug. Development of drug resistance by the virus was not demonstrated during the topical medication and the in vitro test.

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Inhibition of Rhinovirus by Isatin Thiosemicarbazone Analogues

Cited by 41 publications

References 4 publications

Inhibitory effects of antiviral compounds on respiratory syncytial virus replication in vitro

Inhibitory effects of antiviral compounds on respiratory syncytial virus replication in vitro

Antirhinovirus activity of purine nucleoside analogs

Failure of a 3-Substituted Triazinoindole in the Prevention of Experimental Human Rhinovirus Infection

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