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

[Display omitted] •3-hydroxyl enantiopure β-lactams isolated via diastereomeric resolution.•Diastereomeric excess confirmed via quantitative NMR.•Enantiomeric excess > 90 %.•B ring meta hydroxyl substitution yields potent anti-cancer activity in CA-4 resistant colorectal cancer cells.•IC50 of lea...

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Veröffentlicht in:	Bioorganic chemistry 2023-12, Vol.141, p.106877, Article 106877
Hauptverfasser:	McLoughlin, Eavan C., Twamley, Brendan, O'Brien, John E., Hannon Barroeta, Patricia, Zisterer, Daniela M., Meegan, Mary J., O'Boyle, Niamh M.
Format:	Artikel
Sprache:	eng
Schlagworte:	Antiproliferative activity beta-Lactams - chemistry Chiral resolution Colorectal Neoplasms - drug therapy Enantiomers Humans Lactams - pharmacology Microtubules - metabolism Myeloid Cell Leukemia Sequence 1 Protein - metabolism qNMR Structure-Activity Relationship Triple Negative Breast Neoplasms - drug therapy Tubulin - metabolism β-lactams
Online-Zugang:	Volltext
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Zusammenfassung:	[Display omitted] •3-hydroxyl enantiopure β-lactams isolated via diastereomeric resolution.•Diastereomeric excess confirmed via quantitative NMR.•Enantiomeric excess > 90 %.•B ring meta hydroxyl substitution yields potent anti-cancer activity in CA-4 resistant colorectal cancer cells.•IC50 of lead enantiomers
ISSN:	0045-2068 1090-2120 1090-2120
DOI:	10.1016/j.bioorg.2023.106877