New pyrazolone derivatives, synthesis, characterization, and neuroprotective effect against PTZ- induced neuroinflammation in mice
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...
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| Format: | Article |
| Language: | English |
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Mashhad University of Medical Sciences
2022-12-01
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| Series: | Iranian Journal of Basic Medical Sciences |
| Subjects: | |
| Online Access: | https://ijbms.mums.ac.ir/article_21186_e7a6dcef8ca32b3d9c313bb0c12ec2bc.pdf |
| _version_ | 1797977652116586496 |
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| author | Madiha Kanwal Sadia Sarwar Humaira Nadeem Athar Ata Fawad Shah Sumra Malik Saima Maqsood Ghulam Miana |
| author_facet | Madiha Kanwal Sadia Sarwar Humaira Nadeem Athar Ata Fawad Shah Sumra Malik Saima Maqsood Ghulam Miana |
| author_sort | Madiha Kanwal |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-11T05:10:25Z |
| format | Article |
| id | doaj.art-1760c0dfd0dc4d8188b6bf686d7b528d |
| institution | Directory Open Access Journal |
| issn | 2008-3866 2008-3874 |
| language | English |
| last_indexed | 2024-04-11T05:10:25Z |
| publishDate | 2022-12-01 |
| publisher | Mashhad University of Medical Sciences |
| record_format | Article |
| series | Iranian Journal of Basic Medical Sciences |
| spelling | doaj.art-1760c0dfd0dc4d8188b6bf686d7b528d2022-12-25T11:14:14ZengMashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-38662008-38742022-12-0125121424143210.22038/ijbms.2022.62869.1391221186New pyrazolone derivatives, synthesis, characterization, and neuroprotective effect against PTZ- induced neuroinflammation in miceMadiha Kanwal0Sadia Sarwar1Humaira Nadeem2Athar Ata3Fawad Shah4Sumra Malik5Saima Maqsood6Ghulam Miana7Department of Pharmaceutical Chemistry, Riphah International University, Islamabad, Pakistan, 44000Department of Pharmacognosy, Riphah International University, Islamabad, Pakistan, 44000Department of Pharmaceutical Chemistry, Riphah International University, Islamabad, Pakistan, 44000Department of Chemistry, University of Manitoba, CanadaDepartment of Pharmacology, Riphah International University, Islamabad, Pakistan, 44000Department of Pharmaceutical Chemistry, Riphah International University, Islamabad, Pakistan, 44000Department of Pharmaceutical Chemistry, Riphah International University, Islamabad, Pakistan, 44000Department of Pharmaceutical Chemistry, Riphah International University, Islamabad, Pakistan, 44000Objective(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.https://ijbms.mums.ac.ir/article_21186_e7a6dcef8ca32b3d9c313bb0c12ec2bc.pdfanticonvulsantanti-inflammatoryanti-oxidantenzyme-linked - immunosorbent assay (elisa)pyrazolonewestern blot |
| spellingShingle | Madiha Kanwal Sadia Sarwar Humaira Nadeem Athar Ata Fawad Shah Sumra Malik Saima Maqsood Ghulam Miana New pyrazolone derivatives, synthesis, characterization, and neuroprotective effect against PTZ- induced neuroinflammation in mice Iranian Journal of Basic Medical Sciences anticonvulsant anti-inflammatory anti-oxidant enzyme-linked - immunosorbent assay (elisa) pyrazolone western blot |
| title | New pyrazolone derivatives, synthesis, characterization, and neuroprotective effect against PTZ- induced neuroinflammation in mice |
| title_full | New pyrazolone derivatives, synthesis, characterization, and neuroprotective effect against PTZ- induced neuroinflammation in mice |
| title_fullStr | New pyrazolone derivatives, synthesis, characterization, and neuroprotective effect against PTZ- induced neuroinflammation in mice |
| title_full_unstemmed | New pyrazolone derivatives, synthesis, characterization, and neuroprotective effect against PTZ- induced neuroinflammation in mice |
| title_short | New pyrazolone derivatives, synthesis, characterization, and neuroprotective effect against PTZ- induced neuroinflammation in mice |
| title_sort | new pyrazolone derivatives synthesis characterization and neuroprotective effect against ptz induced neuroinflammation in mice |
| topic | anticonvulsant anti-inflammatory anti-oxidant enzyme-linked - immunosorbent assay (elisa) pyrazolone western blot |
| url | https://ijbms.mums.ac.ir/article_21186_e7a6dcef8ca32b3d9c313bb0c12ec2bc.pdf |
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