Synthesis and Anticancer Properties of Oxazepines Related to Azaisoerianin and IsoCoQuines

In this article, we report the synthesis and biological properties of a series of novel oxazepines related to isoCA‐4 having significant antitumor properties. Among them, three oxazepin‐9‐ol derivatives display a nanomolar or a sub‐nanomolar cytotoxicity level against five human cancer cell lines (H...

Full description

Saved in:
Bibliographic Details
Published in:ChemMedChem 2020-08, Vol.15 (16), p.1571-1578
Main Authors: Khelifi, Ilhem, Pecnard, Shannon, Bernadat, Guillaume, Bignon, Jérome, Levaique, Hélène, Dubois, Joëlle, Provot, Olivier, Alami, Mouad
Format: Article
Language:English
Subjects:
Anticancer properties
Biological properties
cancer
Chemical Sciences
Cytotoxicity
isoCA-4
Lead compounds
Molecular modelling
Organic chemistry
oxazepine
quinoline
Synthesis
Toxicity
Tubulin
Tumor cell lines
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:In this article, we report the synthesis and biological properties of a series of novel oxazepines related to isoCA‐4 having significant antitumor properties. Among them, three oxazepin‐9‐ol derivatives display a nanomolar or a sub‐nanomolar cytotoxicity level against five human cancer cell lines (HCT116, U87, A549, MCF7, and K562). It was demonstrated that the lead compound in this series inhibits tubulin assembly with an IC50 value of 1 μM and totally arrests the cellular cycle in the G2/M phase at the low concentration of 5 nM in HCT116 and K562 cells. Molecular modeling studies perfectly corroborates these promising results. Cycle stopper: A series of novel benzo[b][1,4]oxazepines was synthesized, and 1 g was found to be highly cytotoxic at a nanomolar level against five human cancer cell lines and inhibited tubulin assembly. Oxazepinol 1 g blocks the cellular cycle in the G2/M phase. A Molecular docking study shows that 1 g perfectly overlays with isoCA‐4 in β‐tubulin at the colchicine binding site.
ISSN:1860-7179
1860-7187
DOI:10.1002/cmdc.202000197