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New Pharmacological Strategies against Pancreatic Adenocarcinoma: The Multifunctional Thiosemicarbazone FA4

Articolo
Data di Pubblicazione:
2022
Abstract:
A new sigma-2 (σ2) receptor ligand (FA4) was efficiently synthesized and evaluated for cytotoxic, proapoptotic, and antimigratory activity on pancreatic ductal adenocarcinoma (PDAC) primary cell cultures, which restrained the aggressive and chemoresistant behavior of PDAC. This compound showed relevant antiproliferative activity with half maximal inhibitory concentration (IC50) values ranging from 0.701 to 0.825 µM. The cytotoxic activity was associated with induction of apoptosis, resulting in apoptotic indexes higher than those observed after exposure to a clinically relevant concentration of the gemcitabine, the first-line drug used against PDAC. Interestingly, FA4 was also able to significantly inhibit the migration rate of both PDAC-1 and PDAC-2 cells in the scratch wound-healing assay. In conclusion, our results support further studies to improve the library of thiosemicarbazones targeting the σ-2 receptor for a deeper understanding of the relationship between the biological activity of these compounds and the development of more efficient anticancer compounds against PDAC.
Tipologia CRIS:
03A-Articolo su Rivista
Keywords:
Chemoresistance; Migration; Multifunctional thiosemicarbazone; Pancreatic cancer primary cultures; σ-2 receptor ligands; Pancreatic Neoplasms
Elenco autori:
Anobile D.P.; Niso M.; Puerta A.; Fraga Rodrigues S.M.; Abatematteo F.S.; Avan A.; Abate C.; Riganti C.; Giovannetti E.
Autori di Ateneo:
RIGANTI Chiara
Link alla scheda completa:
https://iris.unito.it/handle/2318/1856425
Link al Full Text:
https://iris.unito.it/retrieve/handle/2318/1856425/983454/Anobile,%20MS%20and%20SI%20Molecules,%202022.pdf
Pubblicato in:
MOLECULES
Journal
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