2. Academic Validation
  3. Organotropic dendrons with high potency as HIV-1, HIV-2 and EV-A71 cell entry inhibitors

Organotropic dendrons with high potency as HIV-1, HIV-2 and EV-A71 cell entry inhibitors

  • Eur J Med Chem. 2022 Jul 5;237:114414. doi: 10.1016/j.ejmech.2022.114414.
Olaia Martí-Marí 1,  Belén Martínez-Gualda 1,  Irene Fernández-Barahona 1,  Alberto Mills 2,  Rana Abdelnabi 3,  Sam Noppen 3,  Johan Neyts 3,  Dominique Schols 3,  María-José Camarasa 1,  Fernando Herranz 1,  Federico Gago 4,  Ana San-Félix 5
Affiliations

Affiliations

  • 1 Instituto de Quimica Medica (IQM), CSIC, 28006-Madrid, Spain.
  • 2 Departamento de Ciencias Biomedicas, UAH, Unidad Asociada al CSIC por el IQM, 28805-Alcalá de Henares, Madrid, Spain.
  • 3 Department of Microbiology and Immunology, Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy University of Leuven, B-3000, Leuven, Belgium.
  • 4 Departamento de Ciencias Biomedicas, UAH, Unidad Asociada al CSIC por el IQM, 28805-Alcalá de Henares, Madrid, Spain. Electronic address: federico.gago@uah.es.
  • 5 Instituto de Quimica Medica (IQM), CSIC, 28006-Madrid, Spain. Electronic address: anarosa@iqm.csic.es.
PMID: 35512567 DOI: 10.1016/j.ejmech.2022.114414
Abstract

We have recently described a novel family of compounds of reduced size and dual anti-HIV and anti-EV71 activity that encompasses tripodal and tetrapodal derivatives. The tripodal prototype, AL-470, has a nitro group at the focal point of the central scaffold and three attached tryptophan residues, each of which bearing an isophthaloyl moiety at the C2 position of the indole ring. A nitro to amino substitution has allowed us now to introduce a chemically addressable functionality to perform further structural modifications consisting of both direct and linker-mediated attachment of several aromatic groups, including the Fluorescent Dye Alexa Fluor 647 and the antibody-recruiting 2,4-dinitrophenyl motif. Some of the derivatives turned out to be more potent and selective than AL-470 against HIV-1, HIV-2 and EV-A71. The fluorescent probe demonstrated a specific tropism for intestines and lungs, two important niches for the human microbiome in health and disease.

Keywords

Biodistribution; EV71; Fluorescence imaging; HIV; Viral entry inhibitors.

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