Artículo

Gonzalez, M.M.; Cabrerizo, F.M.; Baiker, A.; Erra-Balsells, R.; Osterman, A.; Nitschko, H.; Vizoso-Pinto, M.G. "β-Carboline derivatives as novel antivirals for herpes simplex virus" (2018) International Journal of Antimicrobial Agents. 52(4):459-468
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Abstract:

Several commercial and novel synthetic β-carbolines (βCs) were evaluated for their antiviral activity against herpes simplex virus type 1 (HSV-1) using an adapted MTS assay. Of 21 drugs tested, although 11 exerted antiviral activity at non-cytotoxic concentrations, only 3 of them [9-methyl-norharmane (9-Me-nHo), 9-methyl-harmane (9-Me-Ho) and 6-methoxy-harmane (6-MeO-Ho)] completely avoided virus-driven cytopathic effects. Half-maximal effective concentrations (EC50 values) (4.9 ± 0.4, 5.9 ± 0.8 and 19.5 ± 0.3 µM, respectively) and selectivity indexes (88.8, 40.2 and 7.0, respectively) of the latter three βCs against HSV-1 were determined by MTS, flow cytometry and plaque reduction assays. The mode of action of these drugs was also evaluated. According to time-of-addition assays, the selected compounds were not virucidal and did not interfere with attachment or penetration of HSV-1, but interfered with later events of virus infection. Western blot studies showed that early and late protein expression was significantly delayed or even suppressed. Herpes simplex virus type 2 (HSV-2) was also inhibited by the selected substances in a similar manner. Interestingly, 6-MeO-Ho, 9-Me-Ho and 9-Me-nHo restricted HSV-1 ICP0 localisation to the nucleus during later stages of infection, possibly affecting its functionality in the cytoplasm where ICP0 normally inhibits antiviral signalling and promotes viral replication. In silico prediction of ADME (Absorption, Distribution, Metabolism and Excretion) properties showed that all compounds fulfilled Lipinski's rule and their calculated absorptions were >95%. © 2018

Registro:

Documento: Artículo
Título:β-Carboline derivatives as novel antivirals for herpes simplex virus
Autor:Gonzalez, M.M.; Cabrerizo, F.M.; Baiker, A.; Erra-Balsells, R.; Osterman, A.; Nitschko, H.; Vizoso-Pinto, M.G.
Filiación:Max von Pettenkofer-Institut, Virology, National Reference Center for Retroviruses, Faculty of Medicine, LMU, Munich, D-80336, Germany
IIB-INTECH-CONICET, Universidad Nacional de San Martín, 7130 Chascomús, Buenos Aires, Argentina
Bavarian Health and Food Safety Authority, Oberschleissheim, Germany
CONICET, Universidad de Buenos Aires, Centro de Investigación en Hidratos de Carbono (CIHIDECAR), Facultad de Ciencias Exactas y Naturales, Pabellón II, 3er P., Ciudad Universitaria, Buenos Aires, 1428, Argentina
German Center for Infection Research (DZIF), partner site Munich, Germany
INSIBIO-CONICET, Departamento Biomédico, Facultad de Medicina, Universidad Nacional de Tucumán, San Miguel de Tucumán4000, Argentina
IIB-INTECH-UNSAM-CONICET (Chascomús), Intendente Marino Km 8.2, CC 164 (7130), Chascomús, Buenos Aires, Argentina
Palabras clave:Alkaloids; Antiherpetic; Antiviral; Carbolines; Herpes simplex virus; ICP0; 1 ethyl norharmane; 6 bromo harmine; 6 chloro harmane; 6 chloro harmine; 6 chloro norharmane; 6 methoxy harmane; 6,8 dibromo harmane; 6,8 dibromo harmine; 6,8 dibromo norharmane; 6,8 dichloro harmane; 6,8 dichloro harmine; 8 bromo harmane; 8 bromo norharmane; 8 chloro harmane; 8 chloro norharmane; 9 methyl harmane; 9 methyl norharmane; antivirus agent; beta carboline; beta carboline derivative; harmaline; harman; harmine; unclassified drug; animal cell; antiviral activity; Article; assay; controlled study; cytotoxicity; drug absorption; drug distribution; drug excretion; drug metabolism; drug selectivity; EC50; flow cytometry; Herpes simplex virus 2; Human alphaherpesvirus 1; MTS assay; nonhuman; plaque reduction assay; priority journal; protein expression; time of addition assay; virus attachment; virus replication; Western blotting
Año:2018
Volumen:52
Número:4
Página de inicio:459
Página de fin:468
DOI: http://dx.doi.org/10.1016/j.ijantimicag.2018.06.019
Título revista:International Journal of Antimicrobial Agents
Título revista abreviado:Int. J. Antimicrob. Agents
ISSN:09248579
CODEN:IAAGE
CAS:beta carboline, 244-63-3; harmaline, 304-21-2; harman, 486-84-0; harmine, 343-27-1, 442-51-3
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_09248579_v52_n4_p459_Gonzalez

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Citas:

---------- APA ----------
Gonzalez, M.M., Cabrerizo, F.M., Baiker, A., Erra-Balsells, R., Osterman, A., Nitschko, H. & Vizoso-Pinto, M.G. (2018) . β-Carboline derivatives as novel antivirals for herpes simplex virus. International Journal of Antimicrobial Agents, 52(4), 459-468.
http://dx.doi.org/10.1016/j.ijantimicag.2018.06.019
---------- CHICAGO ----------
Gonzalez, M.M., Cabrerizo, F.M., Baiker, A., Erra-Balsells, R., Osterman, A., Nitschko, H., et al. "β-Carboline derivatives as novel antivirals for herpes simplex virus" . International Journal of Antimicrobial Agents 52, no. 4 (2018) : 459-468.
http://dx.doi.org/10.1016/j.ijantimicag.2018.06.019
---------- MLA ----------
Gonzalez, M.M., Cabrerizo, F.M., Baiker, A., Erra-Balsells, R., Osterman, A., Nitschko, H., et al. "β-Carboline derivatives as novel antivirals for herpes simplex virus" . International Journal of Antimicrobial Agents, vol. 52, no. 4, 2018, pp. 459-468.
http://dx.doi.org/10.1016/j.ijantimicag.2018.06.019
---------- VANCOUVER ----------
Gonzalez, M.M., Cabrerizo, F.M., Baiker, A., Erra-Balsells, R., Osterman, A., Nitschko, H., et al. β-Carboline derivatives as novel antivirals for herpes simplex virus. Int. J. Antimicrob. Agents. 2018;52(4):459-468.
http://dx.doi.org/10.1016/j.ijantimicag.2018.06.019