Bremer, Paul T. published the artcileNewly Designed Quinolinol Inhibitors Mitigate the Effects of Botulinum Neurotoxin A in Enzymatic, Cell-Based, and ex Vivo Assays, HPLC of Formula: 41910-64-9, the main research area is quinolinol sulfonamide preparation botulinum neurotoxin inhibitor botulism.
Botulinum neurotoxin A (BoNT/A) is one of the most deadly toxins, and is the etiol. agent of the potentially fatal condition, botulism. Herein, the authors investigated 8-hydroxyquinoline (quinolin-8-ol) as a potential inhibitor scaffold for preventing the deadly neurochem. effects of the toxin. Quinolinols are known chelators that can disrupt the BoNT/A metalloprotease zinc-containing active site, thus impeding its proteolysis of the endogenous protein substrate, synaptosomal-associated protein 25 (SNAP-25). Using this information, the structure-activity relationship (SAR) of the quinolinol-5-sulfonamide scaffold was explored through preparation of a crude sulfonamide library, and evaluating the library in a BoNT/A LC enzymic assay. Potency optimization of the sulfonamide hit compounds was undertaken as informed by docking studies, granting a lead compound with a submicromolar Ki. These quinolinol analogs demonstrated inhibitory activity in a cell-based model for SNAP-25 cleavage and an ex vivo assay for BoNT/A-mediated muscle paralysis.
Journal of Medicinal Chemistry published new progress about Botulism. 41910-64-9 belongs to class indole-building-block, name is 4-Chloroindoline, and the molecular formula is C8H8ClN, HPLC of Formula: 41910-64-9.
Referemce:
Indole alkaloid derivatives as building blocks of natural products from Bacillus thuringiensis and Bacillus velezensis and their antibacterial and antifungal activity study,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles