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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...

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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
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cited_by cdi_FETCH-LOGICAL-c577t-dc1b3f6f8ef628506113655fff9ffd8d4001c782e18eefe963999e06aec6a0583
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container_end_page 220358
container_issue 9
container_start_page 220358
container_title Royal Society open science
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creator Viera, Carlos R
Stevens, Bradley T
Viera, Talysa
Zielinski, Cameron
Uranga, Lee A
Rogelj, Snezna
Patidar, Praveen L
Tello-Aburto, Rodolfo
description 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.
doi_str_mv 10.1098/rsos.220358
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subjects Chemistry
multiple myeloma
proteasome inhibitors
β-lactones
title Cystargolide-based amide and ester Pz analogues as proteasome inhibitors and anti-cancer agents
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