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Design, synthesis and in vitro biological evaluation of a novel class of anti-adenovirus agents based on 3-amino-1,2-propanediol.
Mazzotta, Sarah; Berastegui-Cabrera, Judith; Vega-Holm, Margarita; García-Lozano, María Del Rosario; Carretero-Ledesma, Marta; Aiello, Francesca; Vega-Pérez, José Manuel; Pachón, Jerónimo; Iglesias-Guerra, Fernando; Sánchez-Céspedes, Javier.
Afiliação
  • Mazzotta S; Department of Organic and Medicinal Chemistry, Faculty of Pharmacy, University of Seville, E-41071 Seville, Spain; Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Arcavacata di Rende (CS), Italy; Department of Pharmaceutical Sciences, University of Milan, 20133
  • Berastegui-Cabrera J; Unit of Infectious Diseases, Microbiology and Preventive Medicine, Institute of Biomedicine of Seville (IBiS), University Hospital Virgen del Rocío/CSIC/University of Seville, E41013 Seville, Spain.
  • Vega-Holm M; Department of Organic and Medicinal Chemistry, Faculty of Pharmacy, University of Seville, E-41071 Seville, Spain. Electronic address: mvegaholm@us.es.
  • García-Lozano MDR; Department of Organic and Medicinal Chemistry, Faculty of Pharmacy, University of Seville, E-41071 Seville, Spain; Institute of Biomedicine of Seville (IBiS), SeLiver Group, University Hospital Virgen del Rocío/CSIC/University of Seville, E41013 Seville, Spain.
  • Carretero-Ledesma M; Unit of Infectious Diseases, Microbiology and Preventive Medicine, Institute of Biomedicine of Seville (IBiS), University Hospital Virgen del Rocío/CSIC/University of Seville, E41013 Seville, Spain.
  • Aiello F; Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Arcavacata di Rende (CS), Italy.
  • Vega-Pérez JM; Department of Organic and Medicinal Chemistry, Faculty of Pharmacy, University of Seville, E-41071 Seville, Spain.
  • Pachón J; Unit of Infectious Diseases, Microbiology and Preventive Medicine, Institute of Biomedicine of Seville (IBiS), University Hospital Virgen del Rocío/CSIC/University of Seville, E41013 Seville, Spain; Department of Medicine, University of Seville, E-41009 Seville, Spain.
  • Iglesias-Guerra F; Department of Organic and Medicinal Chemistry, Faculty of Pharmacy, University of Seville, E-41071 Seville, Spain. Electronic address: iglesias@us.es.
  • Sánchez-Céspedes J; Unit of Infectious Diseases, Microbiology and Preventive Medicine, Institute of Biomedicine of Seville (IBiS), University Hospital Virgen del Rocío/CSIC/University of Seville, E41013 Seville, Spain. Electronic address: jsanchez-ibis@us.es.
Bioorg Chem ; 114: 105095, 2021 09.
Article em En | MEDLINE | ID: mdl-34175724
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.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Antivirais / Propanolaminas / Desenho de Fármacos / Adenoviridae Idioma: En Ano de publicação: 2021 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Antivirais / Propanolaminas / Desenho de Fármacos / Adenoviridae Idioma: En Ano de publicação: 2021 Tipo de documento: Article