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1,3,4-Oxadiazole and 1,3,4-Thiadiazole Nortopsentin Derivatives against Pancreatic Ductal Adenocarcinoma: Synthesis, Cytotoxic Activity, and Inhibition of CDK1
A new series of nortopsentin analogs, in which the central imidazole ring of the natural lead was replaced by a 1,3,4-oxadiazole or 1,3,4-thiadiazole moiety, was efficiently synthesized. The antiproliferative activity of all synthesized derivatives was evaluated against five pancreatic ductal adenoc...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10381170/ https://www.ncbi.nlm.nih.gov/pubmed/37504943 http://dx.doi.org/10.3390/md21070412 |
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author | Carbone, Daniela Pecoraro, Camilla Panzeca, Giovanna Xu, Geng Roeten, Margot S. F. Cascioferro, Stella Giovannetti, Elisa Diana, Patrizia Parrino, Barbara |
author_facet | Carbone, Daniela Pecoraro, Camilla Panzeca, Giovanna Xu, Geng Roeten, Margot S. F. Cascioferro, Stella Giovannetti, Elisa Diana, Patrizia Parrino, Barbara |
author_sort | Carbone, Daniela |
collection | PubMed |
description | A new series of nortopsentin analogs, in which the central imidazole ring of the natural lead was replaced by a 1,3,4-oxadiazole or 1,3,4-thiadiazole moiety, was efficiently synthesized. The antiproliferative activity of all synthesized derivatives was evaluated against five pancreatic ductal adenocarcinoma (PDAC) cell lines, a primary culture and a gemcitabine-resistant variant. The five more potent compounds elicited EC(50) values in the submicromolar–micromolar range, associated with a significant reduction in cell migration. Moreover, flow cytometric analysis after propidium iodide staining revealed an increase in the G2-M and a decrease in G1-phase, indicating cell cycle arrest, while a specific ELISA demonstrated the inhibition of CDK1 activity, a crucial regulator of cell cycle progression and cancer cell proliferation. |
format | Online Article Text |
id | pubmed-10381170 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-103811702023-07-29 1,3,4-Oxadiazole and 1,3,4-Thiadiazole Nortopsentin Derivatives against Pancreatic Ductal Adenocarcinoma: Synthesis, Cytotoxic Activity, and Inhibition of CDK1 Carbone, Daniela Pecoraro, Camilla Panzeca, Giovanna Xu, Geng Roeten, Margot S. F. Cascioferro, Stella Giovannetti, Elisa Diana, Patrizia Parrino, Barbara Mar Drugs Article A new series of nortopsentin analogs, in which the central imidazole ring of the natural lead was replaced by a 1,3,4-oxadiazole or 1,3,4-thiadiazole moiety, was efficiently synthesized. The antiproliferative activity of all synthesized derivatives was evaluated against five pancreatic ductal adenocarcinoma (PDAC) cell lines, a primary culture and a gemcitabine-resistant variant. The five more potent compounds elicited EC(50) values in the submicromolar–micromolar range, associated with a significant reduction in cell migration. Moreover, flow cytometric analysis after propidium iodide staining revealed an increase in the G2-M and a decrease in G1-phase, indicating cell cycle arrest, while a specific ELISA demonstrated the inhibition of CDK1 activity, a crucial regulator of cell cycle progression and cancer cell proliferation. MDPI 2023-07-19 /pmc/articles/PMC10381170/ /pubmed/37504943 http://dx.doi.org/10.3390/md21070412 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Carbone, Daniela Pecoraro, Camilla Panzeca, Giovanna Xu, Geng Roeten, Margot S. F. Cascioferro, Stella Giovannetti, Elisa Diana, Patrizia Parrino, Barbara 1,3,4-Oxadiazole and 1,3,4-Thiadiazole Nortopsentin Derivatives against Pancreatic Ductal Adenocarcinoma: Synthesis, Cytotoxic Activity, and Inhibition of CDK1 |
title | 1,3,4-Oxadiazole and 1,3,4-Thiadiazole Nortopsentin Derivatives against Pancreatic Ductal Adenocarcinoma: Synthesis, Cytotoxic Activity, and Inhibition of CDK1 |
title_full | 1,3,4-Oxadiazole and 1,3,4-Thiadiazole Nortopsentin Derivatives against Pancreatic Ductal Adenocarcinoma: Synthesis, Cytotoxic Activity, and Inhibition of CDK1 |
title_fullStr | 1,3,4-Oxadiazole and 1,3,4-Thiadiazole Nortopsentin Derivatives against Pancreatic Ductal Adenocarcinoma: Synthesis, Cytotoxic Activity, and Inhibition of CDK1 |
title_full_unstemmed | 1,3,4-Oxadiazole and 1,3,4-Thiadiazole Nortopsentin Derivatives against Pancreatic Ductal Adenocarcinoma: Synthesis, Cytotoxic Activity, and Inhibition of CDK1 |
title_short | 1,3,4-Oxadiazole and 1,3,4-Thiadiazole Nortopsentin Derivatives against Pancreatic Ductal Adenocarcinoma: Synthesis, Cytotoxic Activity, and Inhibition of CDK1 |
title_sort | 1,3,4-oxadiazole and 1,3,4-thiadiazole nortopsentin derivatives against pancreatic ductal adenocarcinoma: synthesis, cytotoxic activity, and inhibition of cdk1 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10381170/ https://www.ncbi.nlm.nih.gov/pubmed/37504943 http://dx.doi.org/10.3390/md21070412 |
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