Synthesis/biological evaluation of hydroxamic acids and their prodrugs as inhibitors for Botulinum neurotoxin A light chain

Bioorganic & Medicinal Chemistry
Hajime SekiKim D Janda

Abstract

Botulinum neurotoxin A (BoNT/A) is the most potent toxin known. Unfortunately, it is also a potential bioweapon in terrorism, which is without an approved therapeutic treatment once cellular intoxication takes place. Previously, we reported how hydroxamic acid prodrug carbamates increased cellular uptake, which translated to successful inhibition of this neurotoxin. Building upon this research, we detail BoNT/A protease molecular modeling studies accompanied by the construction of small library of hydroxamic acids based on 2,4-dichlorocinnamic hydroxamic acid scaffold and their carbamate prodrug derivatization along with the evaluation of these molecules in both enzymatic and cellular models.

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Citations

Jul 30, 2016·Journal of Ethnopharmacology·Chinni YalamanchiliIkhlas A Khan
May 29, 2014·Organic & Biomolecular Chemistry·Giovanna DettoriLidia De Luca
Feb 3, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Kristina KingManfred Jung
Aug 24, 2020·Bioorganic & Medicinal Chemistry·Jordan C ThompsonNicholas T Salzameda
Oct 7, 2017·Journal of Medicinal Chemistry·Paul HermantRebecca Deprez-Poulain
Sep 5, 2020·Journal of Medicinal Chemistry·Lucy LinKim D Janda
Feb 25, 2017·Chemical Reviews·Megan GarlandMatthew Bogyo

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