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© Institut Pasteur
Culture de myotubes murins infectés par le virus de la rage fixe, observée en immunoflorescence indirecte.
Publication : ACS medicinal chemistry letters

DABMA: A Derivative of ABMA with Improved Broad-Spectrum Inhibitory Activity of Toxins and Viruses

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in ACS medicinal chemistry letters - 02 Jul 2019

Wu Y, Pons V, Noël R, Kali S, Shtanko O, Davey RA, Popoff MR, Tordo N, Gillet D, Cintrat JC, Barbier J

Link to Pubmed [PMID] – 31413797

ACS Med Chem Lett 2019 Aug;10(8):1140-1147

The small molecule ABMA has been previously shown to protect cells against multiple toxins and pathogens including virus, intracellular bacteria, and parasite. Its mechanism of action is directly associated with host endolysosomal pathway rather than targeting toxin or pathogen itself. However, the relationship of its broad-spectrum anti-infection activity and chemical structure is not yet resolved. Here, we synthesized a series of derivatives and compared their activities against diphtheria toxin (DT). Dimethyl-ABMA (DABMA), one of the most potent analogs with about 20-fold improvement in protection efficacy against DT, was identified with a similar mechanism of action to ABMA. Moreover, DABMA exhibited enhanced efficacy against toxin B (TcdB), lethal toxin (TcsL), Exotoxin A (PE) as well as Rabies and Ebola viruses. The results revealed a structure-activity relationship of ABMA, which is a starting point for its clinical development as broad-spectrum drug against existing and emerging infectious diseases.

https://www.ncbi.nlm.nih.gov/pubmed/31413797