Synthesis, Cytotoxicity and Anti-Proliferative Activity Against AGS Cells of New 3(2 H )-Pyridazinone Derivatives Endowed with a Piperazinyl Linker

Novel twenty-three 3(2 )-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 nucleus and the additional (un)...

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Published in:Pharmaceuticals (Basel, Switzerland) Switzerland), 2021-02, Vol.14 (3), p.183
Main Authors: Alagöz, Mehmet Abdullah, Özdemir, Zeynep, Uysal, Mehtap, Carradori, Simone, Gallorini, Marialucia, Ricci, Alessia, Zara, Susi, Mathew, Bijo
Format: Article
Language:English
Subjects:
3(2H)-pyridazinone
Bax
fibroblasts
gastric cancer
hydrazone
piperazine
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Summary:Novel twenty-three 3(2 )-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 nucleus 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 doxorubicin as a positive control. Successive analyses revealed that the two most promising representative compounds ( and ) 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 and , 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.
ISSN:1424-8247
1424-8247
DOI:10.3390/ph14030183