Cystargolide-based amide and ester Pz analogues as proteasome inhibitors and anti-cancer agents

A series of cystargolide-based β-lactone analogues containing nitrogen atoms at the Pz portion of the scaffold were prepared and evaluated as proteasome inhibitors, and for their cytotoxicity profile toward several cancer cell lines. Inclusion of one, two or even three nitrogen atoms at the Pz porti...

Full description

Saved in:
Bibliographic Details
Published in:Royal Society open science 2022-09, Vol.9 (9), p.220358-220358
Main Authors: Viera, Carlos R, Stevens, Bradley T, Viera, Talysa, Zielinski, Cameron, Uranga, Lee A, Rogelj, Snezna, Patidar, Praveen L, Tello-Aburto, Rodolfo
Format: Article
Language:English
Subjects:
Chemistry
multiple myeloma
proteasome inhibitors
β-lactones
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:A series of cystargolide-based β-lactone analogues containing nitrogen atoms at the Pz portion of the scaffold were prepared and evaluated as proteasome inhibitors, and for their cytotoxicity profile toward several cancer cell lines. Inclusion of one, two or even three nitrogen atoms at the Pz portion of the cystargolide scaffold is well tolerated, producing analogues with low nanomolar proteasome inhibition activity, in many cases superior to carfilzomib. Additionally, analogue , containing an ester and pyrazine group at Pz, was shown to possess significant activity toward RPMI 8226 cells (IC = 21 nM) and to be less cytotoxic toward the normal tissue model MCF10A cells than carfilzomib.
ISSN:2054-5703
2054-5703
DOI:10.1098/rsos.220358