RT Journal Article
T1 Design, synthesis and in vitro biological evaluation of a novel class of anti-adenovirus agents based on 3-amino-1,2-propanediol.
A1 Mazzotta, Sarah
A1 Berastegui-Cabrera, Judith
A1 Vega-Holm, Margarita
A1 Garcia-Lozano, Maria Del Rosario
A1 Carretero-Ledesma, Marta
A1 Aiello, Francesca
A1 Vega-Perez, Jose Manuel
A1 Pachon, Jeronimo
A1 Iglesias-Guerra, Fernando
A1 Sanchez-Cespedes, Javier
K1 Adenovirus
K1 Aminoalcohol
K1 Antiviral drugs
K1 Carbamate
K1 Ester
K1 Triazole
K1 Urea
AB 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.
PB Academic Press
YR 2021
FD 2021-06-13
LK http://hdl.handle.net/10668/18047
UL http://hdl.handle.net/10668/18047
LA en
NO Mazzotta S, Berastegui-Cabrera J, Vega-Holm M, García-Lozano MDR, Carretero-Ledesma M, Aiello F, et al.  Design, synthesis and in vitro biological evaluation of a novel class of anti-adenovirus agents based on 3-amino-1,2-propanediol. Bioorg Chem. 2021 Sep;114:105095.
NO This work has been supported by Ministerio de Ciencia, Innovación y Universidades, Plan Estatal 2017-2020 Retos - Proyectos I + D + i (PID2019-104767RB-I00); Ministerio de Economía y Competitividad, Plan Nacional I + D + i 2013-2016, Retos-Proyectos (CTQ2016-78580-C2-2-R); Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Economía, Industria y Competitividad, Spanish Network for Research in Infectious Diseases (REIPI RD16/0016/0009), cofinanced by European Development Regional Fund “A way to achieve Europe”, the Instituto de Salud Carlos III, Proyectos de Investigación en Salud (PI17/01055; PI18/01191) and Proyectos de Desarrollo Tecnológico en Salud (DTS17/00130), the Spanish Adenovirus Network (AdenoNet, BIO2015/68990-REDT), and the program “Nicolás Monardes” (C-0059-2018), Servicio Andaluz de Salud, Junta de Andalucía. Authors thank CITIUS (Centro de Investigación, Tecnología e Innovación de la Universidad de Sevilla) for its contribution in recording NMR and Mass spectra and for elemental analysis determination. The authors are especially grateful to Dr. Manuel Angulo Álvarez for his assistance with heteronuclear 2D NMR and NOESY studies.
DS RISalud
RD Apr 10, 2025