Design, synthesis and in vitro biological evaluation of a novel class of anti-adenovirus agents based on 3-amino-1,2-propanediol

Description

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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Ministerio de Ciencia e Innovación PID2019-104767RB-I00

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Ministerio de Economía y Competitividad CTQ2016-78580- C2-2-R

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Spanish Network for Research in Infectious Diseases REIPI RD16/0016/0009

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Proyectos de Desarrollo Tecnológico en Salud DTS17/00130

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Spanish Adenovirus Network AdenoNet BIO2015/68990-REDT

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Junta de Andalucía C-0059-2018

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