Anti-Inflammatory Potentials of β-Ketoester Derivatives of N-Ary Succinimides: In Vitro, In Vivo, and Molecular Docking Studies
Inflammation, being a well-known and complex pathological condition, is always a challenge to the human health. This research work was designed for a rationale-based anti-inflammatory study on β-ketoester derivatives of N-ary succinimides. The compounds (A–D) were synthesized by organocatalytic Mich...
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2022-01-01
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| Series: | Journal of Chemistry |
| Online Access: | http://dx.doi.org/10.1155/2022/8040322 |
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| author | Yahya S. Alqahtani Muhammad Saeed Jan Mater H. Mahnashi Bandar A. Alyami Ali O. Alqarni Umer Rashid Fawad Mahmood Muhammad Tariq Abdul Sadiq |
| author_facet | Yahya S. Alqahtani Muhammad Saeed Jan Mater H. Mahnashi Bandar A. Alyami Ali O. Alqarni Umer Rashid Fawad Mahmood Muhammad Tariq Abdul Sadiq |
| author_sort | Yahya S. Alqahtani |
| collection | DOAJ |
| description | Inflammation, being a well-known and complex pathological condition, is always a challenge to the human health. This research work was designed for a rationale-based anti-inflammatory study on β-ketoester derivatives of N-ary succinimides. The compounds (A–D) were synthesized by organocatalytic Michael addition. The compounds were initially screened for in vitro 5-lipoxygenase (5-LOX) and cyclooxygenase (COX-2) assays. For the in vivo activity, carrageenan-induced paw edema and arachidonic acid-induced ear edema tests were used. Furthermore, different in vivo pathways such as prostaglandins E2, histamine, leukotriene, and bradykinin were studied. The results were supported with molecular docking studies. Among the compounds, D (ethyl 1-(1-benzyl-2,5-dioxopyrrolidin-3-yl)-2-oxocyclohexane-1-carboxylate) at a concentration of 1000 μg/ml showed significant inhibitory effects of 83.67% and 78.12% against COX-2 and 5-LOX in comparison to celecoxib and zileuton, respectively. Similarly, compound D also showed excellent in vivo anti-inflammatory potential. Amongst all the compounds, D demonstrated excellent (55.92 ± 2.95%) anti-inflammatory potential at maximum tested dose (100 mg/kg) which accomplished the highest significance at 4 h following the carrageenan insertion and stayed considerable (∗∗∗P<0.001) till the 5th hour of test sample injection. Compound D also exhibited excellent percent inhibition (63.81 ± 2.24%) at the highest dose in arachidonic acid-induced ear inflammation. On the basis of in vivo and in vitro results, compound D was subjected to various inflammation-causing agents such as histamine, prostaglandins E2, bradykinin, and leukotriene via the mouse paw edema test. Compound D revealed moderate effect (28.10 ± 1.64%) against histamine-induced paw edema while nonsignificant result (9.72 ± 3.125%) was marked for the bradykinin pathway. Compound D showed significance against edematogenic consequence of prostaglandin E2 (56.28–72.03%) and leukotriene (55.13 ± 2.25%) induced inflammation. In summary, our findings recommended that compound D possesses double acting anti-inflammatory properties inhibiting both COX and LOX pathways. Binding orientations and energy values computed via docking simulations support the results of the experimental in vitro evaluation. |
| format | Article |
| id | doaj-art-d9fd576883bf4d27a706b0384ffe4e50 |
| institution | Kabale University |
| issn | 2090-9071 |
| language | English |
| publishDate | 2022-01-01 |
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| spelling | doaj-art-d9fd576883bf4d27a706b0384ffe4e502025-02-03T06:12:24ZengWileyJournal of Chemistry2090-90712022-01-01202210.1155/2022/8040322Anti-Inflammatory Potentials of β-Ketoester Derivatives of N-Ary Succinimides: In Vitro, In Vivo, and Molecular Docking StudiesYahya S. Alqahtani0Muhammad Saeed Jan1Mater H. Mahnashi2Bandar A. Alyami3Ali O. Alqarni4Umer Rashid5Fawad Mahmood6Muhammad Tariq7Abdul Sadiq8Department of Pharmaceutical ChemistryDepartment of PharmacyDepartment of Pharmaceutical ChemistryDepartment of Pharmaceutical ChemistryDepartment of Pharmaceutical ChemistryDepartment of ChemistryDepartment of PharmacyDepartment PCBDepartment of PharmacyInflammation, being a well-known and complex pathological condition, is always a challenge to the human health. This research work was designed for a rationale-based anti-inflammatory study on β-ketoester derivatives of N-ary succinimides. The compounds (A–D) were synthesized by organocatalytic Michael addition. The compounds were initially screened for in vitro 5-lipoxygenase (5-LOX) and cyclooxygenase (COX-2) assays. For the in vivo activity, carrageenan-induced paw edema and arachidonic acid-induced ear edema tests were used. Furthermore, different in vivo pathways such as prostaglandins E2, histamine, leukotriene, and bradykinin were studied. The results were supported with molecular docking studies. Among the compounds, D (ethyl 1-(1-benzyl-2,5-dioxopyrrolidin-3-yl)-2-oxocyclohexane-1-carboxylate) at a concentration of 1000 μg/ml showed significant inhibitory effects of 83.67% and 78.12% against COX-2 and 5-LOX in comparison to celecoxib and zileuton, respectively. Similarly, compound D also showed excellent in vivo anti-inflammatory potential. Amongst all the compounds, D demonstrated excellent (55.92 ± 2.95%) anti-inflammatory potential at maximum tested dose (100 mg/kg) which accomplished the highest significance at 4 h following the carrageenan insertion and stayed considerable (∗∗∗P<0.001) till the 5th hour of test sample injection. Compound D also exhibited excellent percent inhibition (63.81 ± 2.24%) at the highest dose in arachidonic acid-induced ear inflammation. On the basis of in vivo and in vitro results, compound D was subjected to various inflammation-causing agents such as histamine, prostaglandins E2, bradykinin, and leukotriene via the mouse paw edema test. Compound D revealed moderate effect (28.10 ± 1.64%) against histamine-induced paw edema while nonsignificant result (9.72 ± 3.125%) was marked for the bradykinin pathway. Compound D showed significance against edematogenic consequence of prostaglandin E2 (56.28–72.03%) and leukotriene (55.13 ± 2.25%) induced inflammation. In summary, our findings recommended that compound D possesses double acting anti-inflammatory properties inhibiting both COX and LOX pathways. Binding orientations and energy values computed via docking simulations support the results of the experimental in vitro evaluation.http://dx.doi.org/10.1155/2022/8040322 |
| spellingShingle | Yahya S. Alqahtani Muhammad Saeed Jan Mater H. Mahnashi Bandar A. Alyami Ali O. Alqarni Umer Rashid Fawad Mahmood Muhammad Tariq Abdul Sadiq Anti-Inflammatory Potentials of β-Ketoester Derivatives of N-Ary Succinimides: In Vitro, In Vivo, and Molecular Docking Studies Journal of Chemistry |
| title | Anti-Inflammatory Potentials of β-Ketoester Derivatives of N-Ary Succinimides: In Vitro, In Vivo, and Molecular Docking Studies |
| title_full | Anti-Inflammatory Potentials of β-Ketoester Derivatives of N-Ary Succinimides: In Vitro, In Vivo, and Molecular Docking Studies |
| title_fullStr | Anti-Inflammatory Potentials of β-Ketoester Derivatives of N-Ary Succinimides: In Vitro, In Vivo, and Molecular Docking Studies |
| title_full_unstemmed | Anti-Inflammatory Potentials of β-Ketoester Derivatives of N-Ary Succinimides: In Vitro, In Vivo, and Molecular Docking Studies |
| title_short | Anti-Inflammatory Potentials of β-Ketoester Derivatives of N-Ary Succinimides: In Vitro, In Vivo, and Molecular Docking Studies |
| title_sort | anti inflammatory potentials of β ketoester derivatives of n ary succinimides in vitro in vivo and molecular docking studies |
| url | http://dx.doi.org/10.1155/2022/8040322 |
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