Artículo
Design, synthesis and in vitro biological evaluation of a novel class of anti-adenovirus agents based on 3-amino-1,2-propanediol
Autor/es | Mazzotta, Sarah
Berastegui-Cabrera, Judith Vega Holm, Margarita García Lozano, María del Rosario Carretero Ledesma, Marta Claudia Aiello, Francesca Vega Pérez, José Manuel Pachón, Jerónimo Iglesias Guerra, Fernando Sánchez Céspedes, Javier |
Departamento | Universidad de Sevilla. Departamento de Química Orgánica y Farmacéutica |
Fecha de publicación | 2021 |
Fecha de depósito | 2021-07-09 |
Publicado en |
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Premios | Premio Mensual Publicación Científica Destacada de la US. Facultad de Farmacia |
Resumen | Nowadays there is not an effective drug for the treatment of infections caused by human adenovirus (HAdV) which supposes a clinical challenge, especially for paediatric and immunosuppressed patients. Here, we describe the ... Nowadays there is not an effective drug for the treatment of infections caused by human adenovirus (HAdV) which supposes a clinical challenge, especially for paediatric and immunosuppressed patients. Here, we describe the design, synthesis and biological evaluation as anti-adenovirus agents of a new library (57 compounds) of diester, monoester and triazole derivatives based on 3-amino-1,2-propanediol skeleton. Seven compounds (17, 20, 26, 34, 44, 60 and 66) were selected based on their high anti-HAdV activity at low micromolar concentration (IC50 from 2.47 to 5.75 µM) and low cytotoxicity (CC50 from 28.70 to >200 µM). In addition, our mechanistic assays revealed that compounds 20 and 44 might be targeting specifically the HAdV DNA replication process, and compound 66 would be targeting HAdV E1A mRNA transcription. For compounds 17, 20, 34 and 60, the mechanism of action seems to be associated with later steps after HAdV DNA replication. |
Agencias financiadoras | Instituto de Salud Carlos III PI17/01055, PI18/01191 |
Identificador del proyecto | PID2019-104767RB-I00
CTQ2016-78580- C2-2-R REIPI RD16/0016/0009 PI17/01055 PI18/01191 DTS17/00130 BIO2015/68990-REDT C-0059-2018 |
Cita | Mazzotta, S., Berastegui-Cabrera, J., Vega Holm, M., García Lozano, M.d.R., Carretero Ledesma, M.C., Aiello, .,...,Sánchez Céspedes, J. (2021). Design, synthesis and in vitro biological evaluation of a novel class of anti-adenovirus agents based on 3-amino-1,2-propanediol. Bioorganic Chemistry, 114, 105095. |
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