Synthesis by diastereomeric resolution, biochemical evaluation and molecular modelling of chiral 3-hydroxyl b-lactam microtubule-targeting agents for the treatment of triple negative breast and chemoresistant colorectal cancers.
Antiproliferative activity
Chiral resolution
Enantiomers
qNMR
β-lactams
Journal
Bioorganic chemistry
ISSN: 1090-2120
Titre abrégé: Bioorg Chem
Pays: United States
ID NLM: 1303703
Informations de publication
Date de publication:
12 2023
12 2023
Historique:
received:
14
06
2023
revised:
08
09
2023
accepted:
19
09
2023
medline:
3
11
2023
pubmed:
8
10
2023
entrez:
7
10
2023
Statut:
ppublish
Résumé
The synthesis and biochemical activity of a series of chiral trans 3-hydroxyl β-lactams targeting tubulin is described. Synthesis of the series of enantiopure β-lactams was achieved using chiral derivatising reagent N-Boc-l-proline. The absolute configuration was determined as 3S,4S for (+) enantiomer 4EN1 and 3R,4R for (-) enantiomer 4EN2. Antiproliferative studies identified chiral 3S,4S b-lactams with subnanomolar IC
Identifiants
pubmed: 37804699
pii: S0045-2068(23)00538-2
doi: 10.1016/j.bioorg.2023.106877
pii:
doi:
Substances chimiques
Lactams
0
Tubulin
0
Myeloid Cell Leukemia Sequence 1 Protein
0
beta-Lactams
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
106877Subventions
Organisme : Wellcome Trust
ID : 20]4814/Z/16/Z
Pays : United Kingdom
Informations de copyright
Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Niamh O’Boyle reports financial support was provided by Wellcome Trust. Niamh O’Boyle reports financial support was provided by Royal Society of Chemistry. Niamh O’Boyle reports financial support was provided by Trinity College Provosts Teaching Award.