期刊
PHARMACEUTICALS
卷 14, 期 3, 页码 -出版社
MDPI
DOI: 10.3390/ph14030183
关键词
3(2H)-pyridazinone; hydrazone; fibroblasts; gastric cancer; piperazine; Bax; H2O2 release
资金
- Ministero Italiano dell'Universita e della Ricerca (MIUR) [FAR2019]
In this study, novel 23 3(2H)-pyridazinone derivatives were designed and synthesized, with two compounds showing limited cytotoxicity and good anti-proliferative effects. Further experiments revealed that these compounds may exert their effects by inducing oxidative stress.
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 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 (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.
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