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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| Format: | Article |
| Language: | English |
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The Royal Society
2022-09-01
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| Series: | Royal Society Open Science |
| Subjects: | |
| Online Access: | https://royalsocietypublishing.org/doi/10.1098/rsos.220358 |
| _version_ | 1797840287375032320 |
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| author | Carlos R. Viera Bradley T. Stevens Talysa Viera Cameron Zielinski Lee A. Uranga Snezna Rogelj Praveen L. Patidar Rodolfo Tello-Aburto |
| author_facet | Carlos R. Viera Bradley T. Stevens Talysa Viera Cameron Zielinski Lee A. Uranga Snezna Rogelj Praveen L. Patidar Rodolfo Tello-Aburto |
| author_sort | Carlos R. Viera |
| collection | DOAJ |
| 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 8g, containing an ester and pyrazine group at Pz, was shown to possess significant activity toward RPMI 8226 cells (IC50 = 21 nM) and to be less cytotoxic toward the normal tissue model MCF10A cells than carfilzomib. |
| first_indexed | 2024-04-09T16:12:30Z |
| format | Article |
| id | doaj.art-9242af3164b249c0b3881f44a6e4969b |
| institution | Directory Open Access Journal |
| issn | 2054-5703 |
| language | English |
| last_indexed | 2024-04-09T16:12:30Z |
| publishDate | 2022-09-01 |
| publisher | The Royal Society |
| record_format | Article |
| series | Royal Society Open Science |
| spelling | doaj.art-9242af3164b249c0b3881f44a6e4969b2023-04-24T09:15:18ZengThe Royal SocietyRoyal Society Open Science2054-57032022-09-019910.1098/rsos.220358Cystargolide-based amide and ester Pz analogues as proteasome inhibitors and anti-cancer agentsCarlos R. Viera0Bradley T. Stevens1Talysa Viera2Cameron Zielinski3Lee A. Uranga4Snezna Rogelj5Praveen L. Patidar6Rodolfo Tello-Aburto7Department of Chemistry, New Mexico Institute of Mining and Technology, Socorro, NM 87801, USADepartment of Biology, New Mexico Institute of Mining and Technology, Socorro, NM 87801, USADepartment of Chemistry, New Mexico Institute of Mining and Technology, Socorro, NM 87801, USADepartment of Chemical Engineering, New Mexico Institute of Mining and Technology, Socorro, NM 87801, USADepartment of Chemistry and Biochemistry, New Mexico State University, Las Cruces, NM 88003, USADepartment of Biology, New Mexico Institute of Mining and Technology, Socorro, NM 87801, USADepartment of Chemistry, New Mexico Institute of Mining and Technology, Socorro, NM 87801, USADepartment of Chemistry and Biochemistry, New Mexico State University, Las Cruces, NM 88003, USAA 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 8g, containing an ester and pyrazine group at Pz, was shown to possess significant activity toward RPMI 8226 cells (IC50 = 21 nM) and to be less cytotoxic toward the normal tissue model MCF10A cells than carfilzomib.https://royalsocietypublishing.org/doi/10.1098/rsos.220358proteasome inhibitorsβ-lactonesmultiple myeloma |
| spellingShingle | Carlos R. Viera Bradley T. Stevens Talysa Viera Cameron Zielinski Lee A. Uranga Snezna Rogelj Praveen L. Patidar Rodolfo Tello-Aburto Cystargolide-based amide and ester Pz analogues as proteasome inhibitors and anti-cancer agents Royal Society Open Science proteasome inhibitors β-lactones multiple myeloma |
| title | Cystargolide-based amide and ester Pz analogues as proteasome inhibitors and anti-cancer agents |
| title_full | Cystargolide-based amide and ester Pz analogues as proteasome inhibitors and anti-cancer agents |
| title_fullStr | Cystargolide-based amide and ester Pz analogues as proteasome inhibitors and anti-cancer agents |
| title_full_unstemmed | Cystargolide-based amide and ester Pz analogues as proteasome inhibitors and anti-cancer agents |
| title_short | Cystargolide-based amide and ester Pz analogues as proteasome inhibitors and anti-cancer agents |
| title_sort | cystargolide based amide and ester pz analogues as proteasome inhibitors and anti cancer agents |
| topic | proteasome inhibitors β-lactones multiple myeloma |
| url | https://royalsocietypublishing.org/doi/10.1098/rsos.220358 |
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