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

Eur J Med Chem. 2022 Apr 27;237:114414. doi: 10.1016/j.ejmech.2022.114414. Online ahead of print.ABSTRACTWe 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.PMID:35512567 | DOI:10.1016/j.ejmech.2022.114414

Source: European Journal of Medicinal Chemistry - May 5, 2022 Category: Chemistry Authors: Olaia Mart í-Marí Bel én Martínez-Gualda Irene Fern ández-Barahona Alberto Mills Rana Abdelnabi Sam Noppen Johan Neyts Dominique Schols Mar ía-José Camarasa Fernando Herranz Federico Gago Ana San-F élix Source Type: research