Skip to Main content Skip to Navigation
Journal articles

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

Abstract : 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 Clostridium difficile toxin B (TcdB), Clostridium sordellii lethal toxin (TcsL), Pseudomonas 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.
Complete list of metadatas

https://hal-pasteur.archives-ouvertes.fr/pasteur-02453943
Contributor : Nadine Delarue <>
Submitted on : Friday, January 24, 2020 - 10:31:28 AM
Last modification on : Wednesday, July 8, 2020 - 3:37:47 AM

Links full text

Identifiers

Citation

Yu Wu, Valérie Pons, Romain Noël, Sabrina Kali, Olena Shtanko, et al.. DABMA: A Derivative of ABMA with Improved Broad-Spectrum Inhibitory Activity of Toxins and Viruses. ACS Medicinal Chemistry Letters, American Chemical Society, 2019, 10 (8), pp.1140-1147. ⟨10.1021/acsmedchemlett.9b00155⟩. ⟨pasteur-02453943⟩

Share

Metrics

Record views

86