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 adenocarcinoma (PDAC) cell lines, a primary culture and a gemcitabine-resistant variant. The five more potent compounds elicited EC50 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.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2023 |
|---|---|
| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:21 |
|---|---|
| Enthalten in: |
Marine drugs - 21(2023), 7 vom: 19. Juli |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Carbone, Daniela [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 31.07.2023 Date Revised 13.12.2023 published: Electronic Citation Status MEDLINE |
|---|
| doi: |
10.3390/md21070412 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM360048498 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM360048498 | ||
| 003 | DE-627 | ||
| 005 | 20231227131424.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231226s2023 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.3390/md21070412 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1225.xml |
| 035 | |a (DE-627)NLM360048498 | ||
| 035 | |a (NLM)37504943 | ||
| 035 | |a (PII)412 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Carbone, Daniela |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a 1,3,4-Oxadiazole and 1,3,4-Thiadiazole Nortopsentin Derivatives against Pancreatic Ductal Adenocarcinoma |b Synthesis, Cytotoxic Activity, and Inhibition of CDK1 |
| 264 | 1 | |c 2023 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 31.07.2023 | ||
| 500 | |a Date Revised 13.12.2023 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a 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 EC50 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a 1,3,4-oxadiazole | |
| 650 | 4 | |a 1,3,4-thiadiazole | |
| 650 | 4 | |a PDAC antiproliferative activity | |
| 650 | 4 | |a inhibition of CDK1 expression | |
| 650 | 4 | |a inhibition of migration | |
| 650 | 4 | |a nortopsentin analogs | |
| 650 | 7 | |a 1,3,4-thiadiazole |2 NLM | |
| 650 | 7 | |a 14IAC3GH7G |2 NLM | |
| 650 | 7 | |a 1,3,4-oxadiazole |2 NLM | |
| 650 | 7 | |a 20O2F20OUR |2 NLM | |
| 650 | 7 | |a Antineoplastic Agents |2 NLM | |
| 650 | 7 | |a CDK1 protein, human |2 NLM | |
| 650 | 7 | |a EC 2.7.11.22 |2 NLM | |
| 650 | 7 | |a CDC2 Protein Kinase |2 NLM | |
| 650 | 7 | |a EC 2.7.11.22 |2 NLM | |
| 700 | 1 | |a Pecoraro, Camilla |e verfasserin |4 aut | |
| 700 | 1 | |a Panzeca, Giovanna |e verfasserin |4 aut | |
| 700 | 1 | |a Xu, Geng |e verfasserin |4 aut | |
| 700 | 1 | |a Roeten, Margot S F |e verfasserin |4 aut | |
| 700 | 1 | |a Cascioferro, Stella |e verfasserin |4 aut | |
| 700 | 1 | |a Giovannetti, Elisa |e verfasserin |4 aut | |
| 700 | 1 | |a Diana, Patrizia |e verfasserin |4 aut | |
| 700 | 1 | |a Parrino, Barbara |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Marine drugs |d 2007 |g 21(2023), 7 vom: 19. Juli |w (DE-627)NLM179368389 |x 1660-3397 |7 nnns |
| 773 | 1 | 8 | |g volume:21 |g year:2023 |g number:7 |g day:19 |g month:07 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.3390/md21070412 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 21 |j 2023 |e 7 |b 19 |c 07 | ||