Cystargolide-based Amide and Ester Pz Analogues As Proteasome Inhibitors and Anti-cancer Agents

Overview

Journal R Soc Open Sci

Specialty Science

Date 2022 Sep 30

PMID 36177203

Authors

Carlos R Viera

Bradley T Stevens

Talysa Viera

Cameron Zielinski

Lee A Uranga

Snezna Rogelj

Praveen L Patidar

Rodolfo Tello-Aburto

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

Cryptic enzymatic assembly of peptides armed with β-lactone warheads.

Xu G, Torri D, Cuesta-Hoyos S, Panda D, Yates L, Zallot R Nat Chem Biol. 2024; 20(10):1371-1379.

PMID: 38951647 PMC: 11427300. DOI: 10.1038/s41589-024-01657-7.

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

Viera C, Stevens B, Viera T, Zielinski C, Uranga L, Rogelj S R Soc Open Sci. 2022; 9(9):220358.

PMID: 36177203 PMC: 9515629. DOI: 10.1098/rsos.220358.

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