Synthesis, Cytotoxicity and Anti-Proliferative Activity against AGS Cells of New 3(2<i>H</i>)-Pyridazinone Derivatives Endowed with a Piperazinyl Linker
Novel twenty-three 3(2<i>H</i>)-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...
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| Main Authors: | , , , , , , , |
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| Format: | Book |
| Published: |
MDPI AG,
2021-02-01T00:00:00Z.
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| Online Access: | Connect to this object online. |
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| Summary: | Novel twenty-three 3(2<i>H</i>)-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 (<b>12</b> and <b>22</b>) 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 <b>12</b> and <b>22</b>, 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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| Item Description: | 10.3390/ph14030183 1424-8247 |