A New N-Substituted 1<i>H</i>-Isoindole-1,3(2<i>H</i>)-Dione Derivative—Synthesis, Structure and Affinity for Cyclooxygenase Based on In Vitro Studies and Molecular Docking
Isoindoline-1,3-dione derivatives constitute an important group of medicinal substances. In this study, nine new 1<i>H</i>-isoindole-1,3(2<i>H</i>)-dione derivatives and five potential pharmacophores were obtained in good yield (47.24–92.91%). The structure of the new imides...
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MDPI AG
2021-07-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/14/7678 |
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| author | Dominika Szkatuła Edward Krzyżak Paulina Stanowska Magdalena Duda Benita Wiatrak |
| author_facet | Dominika Szkatuła Edward Krzyżak Paulina Stanowska Magdalena Duda Benita Wiatrak |
| author_sort | Dominika Szkatuła |
| collection | DOAJ |
| description | Isoindoline-1,3-dione derivatives constitute an important group of medicinal substances. In this study, nine new 1<i>H</i>-isoindole-1,3(2<i>H</i>)-dione derivatives and five potential pharmacophores were obtained in good yield (47.24–92.91%). The structure of the new imides was confirmed by the methods of elemental and spectral analysis: FT–IR, H NMR, and MS. Based on the obtained results of ESI–MS the probable path of the molecules decay and the hypothetical structure of the resulting pseudo-molecular ions have been proposed. The physicochemical properties of the new phthalimides were determined on the basis of Lipiński’s rule. The biological properties were determined in terms of their cyclooxygenase (COX) inhibitory activity. Three compounds showed greater inhibition of COX-2, three compounds inhibited COX-1 more strongly than the reference compound meloxicam. From the obtained results, the affinity ratio COX-2/COX-1 was calculated. Two compounds had a value greater than that of meloxicam. All tested compounds showed oxidative or nitrosan stress (ROS and RNS) scavenging activity. The degree of chromatin relaxation outside the cell nucleus was lower than the control after incubation with all test compounds. The newly synthesized phthalimide derivatives showed no cytotoxic activity in the concentration range studied (10–90 µM). A molecular docking study was used to determined interactions inside the active site of cyclooxygenases. |
| first_indexed | 2024-03-10T09:36:29Z |
| format | Article |
| id | doaj.art-9e0296a474984f22b3203d9580cd6510 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T09:36:29Z |
| publishDate | 2021-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-9e0296a474984f22b3203d9580cd65102023-11-22T04:02:28ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-07-012214767810.3390/ijms22147678A New N-Substituted 1<i>H</i>-Isoindole-1,3(2<i>H</i>)-Dione Derivative—Synthesis, Structure and Affinity for Cyclooxygenase Based on In Vitro Studies and Molecular DockingDominika Szkatuła0Edward Krzyżak1Paulina Stanowska2Magdalena Duda3Benita Wiatrak4Department of Medicinal Chemistry, Wroclaw Medical University, Borowska 211, 50-556 Wroclaw, PolandDepartment of Inorganic Chemistry, Wroclaw Medical University, ul. Borowska 211a, 50-556 Wrocław, PolandStudent Scientific Club of Medicinal Chemistry, Wroclaw Medical University, Borowska 211, 50-556 Wroclaw, PolandStudent Scientific Club of Medicinal Chemistry, Wroclaw Medical University, Borowska 211, 50-556 Wroclaw, PolandDepartment of Pharmacology, Faculty of Medicine, Wroclaw Medical University, Mikulicza-Radeckiego 2, 50-345 Wroclaw, PolandIsoindoline-1,3-dione derivatives constitute an important group of medicinal substances. In this study, nine new 1<i>H</i>-isoindole-1,3(2<i>H</i>)-dione derivatives and five potential pharmacophores were obtained in good yield (47.24–92.91%). The structure of the new imides was confirmed by the methods of elemental and spectral analysis: FT–IR, H NMR, and MS. Based on the obtained results of ESI–MS the probable path of the molecules decay and the hypothetical structure of the resulting pseudo-molecular ions have been proposed. The physicochemical properties of the new phthalimides were determined on the basis of Lipiński’s rule. The biological properties were determined in terms of their cyclooxygenase (COX) inhibitory activity. Three compounds showed greater inhibition of COX-2, three compounds inhibited COX-1 more strongly than the reference compound meloxicam. From the obtained results, the affinity ratio COX-2/COX-1 was calculated. Two compounds had a value greater than that of meloxicam. All tested compounds showed oxidative or nitrosan stress (ROS and RNS) scavenging activity. The degree of chromatin relaxation outside the cell nucleus was lower than the control after incubation with all test compounds. The newly synthesized phthalimide derivatives showed no cytotoxic activity in the concentration range studied (10–90 µM). A molecular docking study was used to determined interactions inside the active site of cyclooxygenases.https://www.mdpi.com/1422-0067/22/14/7678phthalimidearylpiperazinecyclooxygenase inhibitionmolecular docking |
| spellingShingle | Dominika Szkatuła Edward Krzyżak Paulina Stanowska Magdalena Duda Benita Wiatrak A New N-Substituted 1<i>H</i>-Isoindole-1,3(2<i>H</i>)-Dione Derivative—Synthesis, Structure and Affinity for Cyclooxygenase Based on In Vitro Studies and Molecular Docking International Journal of Molecular Sciences phthalimide arylpiperazine cyclooxygenase inhibition molecular docking |
| title | A New N-Substituted 1<i>H</i>-Isoindole-1,3(2<i>H</i>)-Dione Derivative—Synthesis, Structure and Affinity for Cyclooxygenase Based on In Vitro Studies and Molecular Docking |
| title_full | A New N-Substituted 1<i>H</i>-Isoindole-1,3(2<i>H</i>)-Dione Derivative—Synthesis, Structure and Affinity for Cyclooxygenase Based on In Vitro Studies and Molecular Docking |
| title_fullStr | A New N-Substituted 1<i>H</i>-Isoindole-1,3(2<i>H</i>)-Dione Derivative—Synthesis, Structure and Affinity for Cyclooxygenase Based on In Vitro Studies and Molecular Docking |
| title_full_unstemmed | A New N-Substituted 1<i>H</i>-Isoindole-1,3(2<i>H</i>)-Dione Derivative—Synthesis, Structure and Affinity for Cyclooxygenase Based on In Vitro Studies and Molecular Docking |
| title_short | A New N-Substituted 1<i>H</i>-Isoindole-1,3(2<i>H</i>)-Dione Derivative—Synthesis, Structure and Affinity for Cyclooxygenase Based on In Vitro Studies and Molecular Docking |
| title_sort | new n substituted 1 i h i isoindole 1 3 2 i h i dione derivative synthesis structure and affinity for cyclooxygenase based on in vitro studies and molecular docking |
| topic | phthalimide arylpiperazine cyclooxygenase inhibition molecular docking |
| url | https://www.mdpi.com/1422-0067/22/14/7678 |
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