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Iranian Journal of Basic Medical Sciences، جلد ۲۵، شماره ۱۲، صفحات ۱۴۲۴-۱۴۳۲
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عنوان انگلیسی New pyrazolone derivatives, synthesis, characterization, and neuroprotective effect against PTZ- induced neuroinflammation in mice
چکیده انگلیسی مقاله Objective(s): The study was aimed at synthesis of the new derivatives of the pyrazolone nucleus, and their spectroscopic and pharmacological analysis and evaluation. Materials and Methods: Three series of compounds, with 2-picolinic acid (I a-d), 3-picolinic acid (II a-d), and 4-picolinic acid (III a-d) were synthesized and characterized by FT-IR, 1HNMR, 13C NMR, elemental, and melting points. The new compounds were then evaluated for their anti-oxidant, anti-inflammatory, and anti-epileptic potential. The hind paw edema model was used to screen anti-inflammatory potential, while the anticonvulsant effect was evaluated by employing the acute model of anti-epileptic activity. The in vivo anti-oxidant potential was determined through glutathione (GSH), glutathione-S-transferase (GST), catalase, and lipid peroxidase enzyme (LPO) assays. The expression of key biomarkers involved in inflammation and neuroprotection, including tumor necrotic factors alpha (TNF-α) and phosphorylated nuclear factor kappa B (NF-κB), was detected through enzyme-linked immunosorbent assay (ELISA) and Western blot analysis. Results: The tested compounds showed anti-oxidant potential. The selected compounds exhibited good anti-inflammatory potential. The PTZ-induced elevation of these inflammatory mediators and oxidative stress were ameliorated significantly by the selected compound Ic. Results of molecular analysis (ELISA and Western blot analysis) for potent compound Ic showed a prominent inhibitory effect against neuroinflammatory mediators, including TNF-α and NF-κB. Conclusion: It is concluded that the derivative Ic ameliorated PTZ-induced seizures, oxidative stress, and inflammatory cascades by regulating the NF-κB/ TNF-α/ROS pathway.
کلیدواژه‌های انگلیسی مقاله Anticonvulsant, Anti-inflammatory, Anti-oxidant, Enzyme-linked - immunosorbent assay (ELISA), Pyrazolone, Western blot
نویسندگان مقاله | Madiha Kanwal
Department of Pharmaceutical Chemistry, Riphah International University, Islamabad, Pakistan, 44000


| Sadia Sarwar
Department of Pharmacognosy, Riphah International University, Islamabad, Pakistan, 44000


| Humaira Nadeem
Department of Pharmaceutical Chemistry, Riphah International University, Islamabad, Pakistan, 44000


| Athar Ata
Department of Chemistry, University of Manitoba, Canada


| Fawad Shah
Department of Pharmacology, Riphah International University, Islamabad, Pakistan, 44000


| Sumra Malik
Department of Pharmaceutical Chemistry, Riphah International University, Islamabad, Pakistan, 44000


| Saima Maqsood
Department of Pharmaceutical Chemistry, Riphah International University, Islamabad, Pakistan, 44000


| Ghulam Miana
Department of Pharmaceutical Chemistry, Riphah International University, Islamabad, Pakistan, 44000
نشانی اینترنتی https://ijbms.mums.ac.ir/article_21186.html
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