Actividad antiherpética in vitro de brassinosteroides obtenidos por síntesis química
The brassinosteroids are a group of steroids widely distributed in plants which are essential for their growth and development. These compounds have a potential use in agriculture due to their capacity to improve the yield and quality of the cultures. The natural brassinosteroids identified so far...
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| Formato: | Tesis |
| Lenguaje: | Español |
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Universidad de Belgrano. Facultad de Ciencias Exactas y Naturales. Farmacia
2015
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| Acceso en línea: | http://repositorio.ub.edu.ar/handle/123456789/5101 |
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| Sumario: | The brassinosteroids are a group of steroids widely distributed in plants which are essential for their
growth and development. These compounds have a potential use in agriculture due to their capacity to
improve the yield and quality of the cultures. The natural brassinosteroids identified so far and their synthetic
analogues have in common a 5-?-cholestane skeleton and their structural variations come from the type,
position and stereochemistry of functional groups present in the skeleton and the side chain. Four years ago
antiviral properties of brassinosteroids were not known.
In this work we have compiled and analysed information about the antiherpetic properties in vitro of
brassinosteroids obtained by chemical synthesis based on recent investigations. In an early study the
antiherpetic activity of 12 brassinosteroid derivatives (1a - 6b) was evaluated against the strains F and B
2006 of herpes simplex virus type 1 (HSV-1), employing a plaque reduction assay to determine the EC50
(50% antiviral effective concentration). The compounds resulted to be equally active against both strains of
HSV-1. In a later work, other 26 brassinosteroid derivatives (7 - 32) were evaluated against HSV-1 (strain F)
and HSV-2 (strain G) via a virus yield reduction assay. Furthermore, the anti-HSV-1 activity of derivatives 1a
- 6b and the anti-HSV-2 activity of compound 6b were determined using the latter method. Stigmasterol, a
natural sterol from which the tested brassinosteroids were derived, and acyclovir were used as controls. The
CC50 (50% cytotoxic concentration) values were determined by the MTT colorimetric assay using confluent
non-growing cellular cultures. The selectivity indexes (SI) were calculated as the ratio CC50 / EC50. Among
the compounds evaluated, the brassinosteroids 6b, 7b and 12b were in general the most active ones with SI
values of 100, 80 and 109 for HSV-1 and 71, 40 and 27 for HSV-2, respectively. From the results obtained in
these investigations, structure-activity relationship (SAR) studies could be developed for the different brassinosteroid
derivatives against HSV-1 and HSV-2.
The antiviral effect of the brassinosteroid derivatives assayed was not due to direct inactivation, showing
that a step in the viral replicative cycle was being altered. Concerning the action mode of brassinosteroids,
the experiments of viral adsoption, viral penetration and time-of-addition of compound 6b suggest that a late
step in HSV-1 multiplication was being affected, indicating that the action mechanism would be different from
that of acyclovir, active drug against HSV used in clinic.
The brassinosteroids evaluated in this study represent a new class of compounds that has been found to
be moderately active against HSV-1 and HSV-2, at concentrations that were not toxic to the host cells.
Based on structure-activity relationship (SAR) studies and quantitative structure-activity relationship (QSAR)
studies, a new class of potent and selective HSV inhibitors will be searched. |
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