Novel twenty−three 3(2H)−pyridazinone derivatives were designed and synthesized based on the chemical requirements related to the anti−proliferative effects previously demonstrated within this scaffold. The introduction of a piperazinyl linker between the pyridazinone nu-cleus and the additional (un)substituted phenyl group led to some compounds endowed with a limited cytotoxicity against human gingival fibroblasts (HGFs) and good anti−proliferative effects against gastric adenocarcinoma cells (AGS) as evaluated by MTT and LDH assays, using doxorubi-cin as a positive control. Successive analyses revealed that the two most promising representative compounds (12 and 22) could exert their effects by inducing oxidative stress as demonstrated by the hydrogen peroxide release and the morphological changes (cell blebbing) revealed by light microscopy analysis after the haematoxylin−eosin staining. Moreover, to further assess the apoptotic process induced by compounds 12 and 22, Bax expression was measured by flow cytometry. These findings enlarged our knowledge of the structural requirements in this scaffold to display valuable biological effects against cancerous cell lines.

Synthesis, cytotoxicity and anti−proliferative activity against ags cells of new 3(2h)−pyridazinone derivatives endowed with a piperazinyl linker

Carradori S.
;
Gallorini M.;Ricci A.;Zara S.;
2021-01-01

Abstract

Novel twenty−three 3(2H)−pyridazinone derivatives were designed and synthesized based on the chemical requirements related to the anti−proliferative effects previously demonstrated within this scaffold. The introduction of a piperazinyl linker between the pyridazinone nu-cleus and the additional (un)substituted phenyl group led to some compounds endowed with a limited cytotoxicity against human gingival fibroblasts (HGFs) and good anti−proliferative effects against gastric adenocarcinoma cells (AGS) as evaluated by MTT and LDH assays, using doxorubi-cin as a positive control. Successive analyses revealed that the two most promising representative compounds (12 and 22) could exert their effects by inducing oxidative stress as demonstrated by the hydrogen peroxide release and the morphological changes (cell blebbing) revealed by light microscopy analysis after the haematoxylin−eosin staining. Moreover, to further assess the apoptotic process induced by compounds 12 and 22, Bax expression was measured by flow cytometry. These findings enlarged our knowledge of the structural requirements in this scaffold to display valuable biological effects against cancerous cell lines.
File in questo prodotto:
File Dimensione Formato  
pharmaceuticals-14-00183-v4.pdf

accesso aperto

Tipologia: PDF editoriale
Dimensione 7.34 MB
Formato Adobe PDF
7.34 MB Adobe PDF Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11564/748350
Citazioni
  • ???jsp.display-item.citation.pmc??? 3
  • Scopus 11
  • ???jsp.display-item.citation.isi??? 11
social impact