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Synthesis and evaluation of library of betulin derivatives against the botulinum neurotoxin A protease
- Source :
-
Bioorganic & Medicinal Chemistry Letters . Apr2011, Vol. 21 Issue 8, p2229-2231. 3p. - Publication Year :
- 2011
-
Abstract
- Abstract: Botulinum neurotoxins (BoNTs) are the most toxic proteins currently known. Current treatments for botulinum poisoning are all protein based with a limited window of opportunity. Inhibition of the BoNT light chain protease (LC) has emerged as a new therapeutic strategy for the treatment of botulism as it may provide an effective post-exposure remedy. As such, a small library of 40 betulin derivatives was synthesized and screened against the light chain of BoNT serotype A (LC/A); five positive hits (IC50 <100μM) were uncovered. Detailed evaluation of inhibition mechanism of three most active compounds revealed a competitive model, with sub-micromolar K i value for the best inhibitor (7). Unfortunately, an in vitro cell-based assay did not show any protection of rat cerebellar neurons against BoNT/A intoxication by 7. [Copyright &y& Elsevier]
Details
- Language :
- English
- ISSN :
- 0960894X
- Volume :
- 21
- Issue :
- 8
- Database :
- Academic Search Index
- Journal :
- Bioorganic & Medicinal Chemistry Letters
- Publication Type :
- Academic Journal
- Accession number :
- 59773387
- Full Text :
- https://doi.org/10.1016/j.bmcl.2011.02.115