“Pyridopyridazine”: A Versatile Nucleus in Pharmaceutical Field

Ibrahim, Mohamed A.; Elmenoufy, Ahmed H.; Elagawany, Mohamed; Ghoneim, Mohammed M.; Moawad, Alaa

doi:10.4236/jbm.2015.310008

Cited by 6 publications

(6 citation statements)

References 18 publications

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“…During the last decade, many interesting functional structures of pharmacophore moieties in pyridazinones made them an attractive source of new active derivatives . Combination of benzofuran and pyridazinones has led to good results for the first time.…”

Section: Discussionmentioning

confidence: 99%

Cytotoxicity of new pyridazin‐3(2H)‐one derivatives orchestrating oxidative stress in human triple‐negative breast cancer (MDA‐MB‐468)

Bouchmaa

Mrid²,

Boukharsa

et al. 2018

Archiv der Pharmazie

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Triple-negative breast cancer (TNBC) is a complex and aggressive subtype of breast cancer characterized by high morbidity and mortality. In the absence of targeted therapy, only chemotherapy is available in this case of cancer. The current study investigated the antitumor effect of new pyridazin-3(2H)-one derivatives on the human TNBC cell line, MD-MB-468. The in vitro cytotoxic activities were investigated using the tetrazolium-based MTT assay. Lipid peroxidation, H 2 O 2 content, and the specific activities of antioxidant enzymes were also determined. Two molecules, 6f and 7h, were found to be selectively highly active against tumor cells with IC 50 values of 3.12 and 4.9 µM, respectively. Furthermore, cells exposed to 6f showed a significant increase in H 2 O 2 and lipid peroxidation levels, accompanied by a decrease in the enzyme activities of glutathione reductase (GR) and thioredoxin reductase (TrxR). The cytotoxicity of the compound 6f may improve the therapeutic efficacy of the current treatment for TNBC via the inhibition of GR and TrxR activities.anticancer agent, cytotoxicity, oxidative stress, pyridazin-(2H)-3-ones, triple-negative breast cancer

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Section: Discussionmentioning

confidence: 99%

Cytotoxicity of new pyridazin‐3(2H)‐one derivatives orchestrating oxidative stress in human triple‐negative breast cancer (MDA‐MB‐468)

Bouchmaa

Mrid²,

Boukharsa

et al. 2018

Archiv der Pharmazie

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“…During the last decade, many interesting functional structure of pharmacophore moieties in pyridazinones makes them an attractive source of new active derivatives [24,37]. Combination of benzofuran and pyridazinones has led to good results for the first time.…”

Section: Discussionmentioning

confidence: 99%

Reactive Oxygen Species-Mediated Apoptosis and Cytotoxicity of Newly Synthesized Pyridazin-3-Ones In P815 (Murin Mastocytoma) Cell Line

et al. 2019

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Background In cancer cells, the intracellular antioxidant capacity and the redox homeostasis are mainly maintained by the glutathione- and thioredoxin-dependent systems which are considered as promising targets for anticancer drugs. Pyridazinones constitute an interesting source of heterocyclic compounds for drug discovery. The present investigation focused on studying the in-vitro antitumor activity of newly synthesized Pyridazin-3(2h)-ones derivatives against P815 (Murin mastocytoma) cell line. Methods The in-vitro cytotoxic activities were investigated toward the P815 cell line using tetrazolium-based MTT assay. Lipid peroxidation and the specific activities of antioxidant enzymes were also determined. Results The newly compounds had a selective dose-dependent cytotoxic effect without affecting normal cells (PBMCs). Apoptosis was further confirmed through the characteristic apoptotic morphological changes and DNA fragmentation. Two compounds (6f and 7h) were highly cytotoxic and were submitted to extend biological testing to determine the likely mechanisms of their cytotoxicity. Results showed that these molecules may induce cytotoxicity via disturbing the redox homeostasis. Importantly, the anticancer activity of 6f and 7h could be due to the intracellular reactive oxygen species hypergeneration through significant loss of glutathione reductase and thioredoxin reductase activities. This eventually leads to oxidative stress-mediated P815 cell apoptosis. Furthermore, the co-administration of 6f or 7h with Methotrexate exhibited a synergistic cytotoxic effect. Conclusions considering their significant anticancer activity and chemosensitivity, 6f and 7h may improve the therapeutic efficacy of the current treatment for cancer.

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“…Acrifoline (IV), a quinolinone fused with benzopyran, and pyridazine (V), pyridine fused with pyridazine scaffolds, have been found to be effective as anticancer, antidiabetic, analgesic, anti-inflammatory and anti-hypertensive agents [13]. However, there is a lack of structural similarity among the known DYRK1A inhibitors derived from natural products, except for the common feature of a fused heterocyclic system with three to four fused rings highlights the need for our current study.…”

Section: Introductionmentioning

confidence: 96%

Anticancer and Antimicrobial Screening of Novel Pyrazolo[2,3-c]pyridopyridazine Analogues: Synthesis, Spectral Characterization, Molecular Docking and Dynamics Studies

BHARDWAJ,

KUMAR,

TONK

2023

ajc

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A major threat in cancer management is the development of drug resistance and gene mutations. Serine threonine kinases like DYRK1A pathway are potential targets for cancer therapies. In this work, a new series of seven pyrazolo[2,3-c]pyridopyridazine analogs were synthesized and characterized by spectroscopic methods. Three compounds were evaluated for in-vitro anticancer activity following 60 cell lines protocol of NCI, USA and for antimicrobial activity against Gram-negative and Gram-positive bacteria. All the compounds exhibited moderate to good antibacterial activity, while compounds 4a, 4b and 4d showed moderate responses against leukemia, ovarian cancer, and prostate cancer cell lines in anti-proliferative studies.

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“Pyridopyridazine”: A Versatile Nucleus in Pharmaceutical Field

Cited by 6 publications

References 18 publications

Cytotoxicity of new pyridazin‐3(2H)‐one derivatives orchestrating oxidative stress in human triple‐negative breast cancer (MDA‐MB‐468)

Cytotoxicity of new pyridazin‐3(2H)‐one derivatives orchestrating oxidative stress in human triple‐negative breast cancer (MDA‐MB‐468)

Reactive Oxygen Species-Mediated Apoptosis and Cytotoxicity of Newly Synthesized Pyridazin-3-Ones In P815 (Murin Mastocytoma) Cell Line

Anticancer and Antimicrobial Screening of Novel Pyrazolo[2,3-c]pyridopyridazine Analogues: Synthesis, Spectral Characterization, Molecular Docking and Dynamics Studies

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