Synthesis of New Tricyclic 1,2-Thiazine Derivatives with Anti-Inflammatory Activity
New, tricyclic compounds containing a sulfonyl moiety in their structure, as potential safer COX inhibitors, were designed and synthesized. New derivatives have three conjugated rings and a sulfonyl group. A third ring, i.e., an oxazine, oxazepine or oxazocin, has been added to the 1,2-benzothiazine...
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| Format: | Article |
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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/1422-0067/22/15/7818 |
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| author | Jadwiga Maniewska Benita Wiatrak Żaneta Czyżnikowska Berenika M. Szczęśniak-Sięga |
| author_facet | Jadwiga Maniewska Benita Wiatrak Żaneta Czyżnikowska Berenika M. Szczęśniak-Sięga |
| author_sort | Jadwiga Maniewska |
| collection | DOAJ |
| description | New, tricyclic compounds containing a sulfonyl moiety in their structure, as potential safer COX inhibitors, were designed and synthesized. New derivatives have three conjugated rings and a sulfonyl group. A third ring, i.e., an oxazine, oxazepine or oxazocin, has been added to the 1,2-benzothiazine skeleton. Their anti-COX-1/COX-2 and cytotoxic effects in vitro on NHDF cells, together with the ability to interact with model membranes and the influence on reactive oxygen species and nitric oxide, were studied. Additionally, a molecular docking study was performed to understand the binding interaction of the compounds with the active site of cyclooxygenases. For the abovementioned biological evaluation of new tricyclic 1,2-benzothiazine derivatives, the following techniques and procedures were employed: the differential scanning calorimetry, the COX colorimetric inhibitor screening assay, the MTT, DCF-DA and Griess assays. All of the compounds studied demonstrated preferential inhibition of COX-2 compared to COX-1. Moreover, all the examined tricyclic 1,2-thiazine derivatives interacted with the phospholipid model membranes. Finally, they neither have cytotoxic potency, nor demonstrate significant influence on the level of reactive oxygen species or nitric oxide. Overall, the tricyclic 1,2-thiazine derivatives are good starting points for future pharmacological tests as a group of new anti-inflammatory agents. |
| first_indexed | 2024-03-10T09:15:48Z |
| format | Article |
| id | doaj.art-533533fe86cd4a8296eabbe8191f847f |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T09:15:48Z |
| publishDate | 2021-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-533533fe86cd4a8296eabbe8191f847f2023-11-22T05:38:52ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-07-012215781810.3390/ijms22157818Synthesis of New Tricyclic 1,2-Thiazine Derivatives with Anti-Inflammatory ActivityJadwiga Maniewska0Benita Wiatrak1Żaneta Czyżnikowska2Berenika M. Szczęśniak-Sięga3Department of Medicinal Chemistry, Faculty of Pharmacy, Wroclaw Medical University, Borowska 211, 50-556 Wrocław, PolandDepartment of Pharmacology, Faculty of Medicine, Wroclaw Medical University, J. Mikulicza-Radeckiego 2, 50-345 Wrocław, PolandDepartment of Inorganic Chemistry, Faculty of Pharmacy, Wroclaw Medical University, Borowska 211a, 50-556 Wrocław, PolandDepartment of Medicinal Chemistry, Faculty of Pharmacy, Wroclaw Medical University, Borowska 211, 50-556 Wrocław, PolandNew, tricyclic compounds containing a sulfonyl moiety in their structure, as potential safer COX inhibitors, were designed and synthesized. New derivatives have three conjugated rings and a sulfonyl group. A third ring, i.e., an oxazine, oxazepine or oxazocin, has been added to the 1,2-benzothiazine skeleton. Their anti-COX-1/COX-2 and cytotoxic effects in vitro on NHDF cells, together with the ability to interact with model membranes and the influence on reactive oxygen species and nitric oxide, were studied. Additionally, a molecular docking study was performed to understand the binding interaction of the compounds with the active site of cyclooxygenases. For the abovementioned biological evaluation of new tricyclic 1,2-benzothiazine derivatives, the following techniques and procedures were employed: the differential scanning calorimetry, the COX colorimetric inhibitor screening assay, the MTT, DCF-DA and Griess assays. All of the compounds studied demonstrated preferential inhibition of COX-2 compared to COX-1. Moreover, all the examined tricyclic 1,2-thiazine derivatives interacted with the phospholipid model membranes. Finally, they neither have cytotoxic potency, nor demonstrate significant influence on the level of reactive oxygen species or nitric oxide. Overall, the tricyclic 1,2-thiazine derivatives are good starting points for future pharmacological tests as a group of new anti-inflammatory agents.https://www.mdpi.com/1422-0067/22/15/7818synthesistricyclic compounds1,2-thiazinecyclooxygenase inhibitionmodel membraneDSC |
| spellingShingle | Jadwiga Maniewska Benita Wiatrak Żaneta Czyżnikowska Berenika M. Szczęśniak-Sięga Synthesis of New Tricyclic 1,2-Thiazine Derivatives with Anti-Inflammatory Activity International Journal of Molecular Sciences synthesis tricyclic compounds 1,2-thiazine cyclooxygenase inhibition model membrane DSC |
| title | Synthesis of New Tricyclic 1,2-Thiazine Derivatives with Anti-Inflammatory Activity |
| title_full | Synthesis of New Tricyclic 1,2-Thiazine Derivatives with Anti-Inflammatory Activity |
| title_fullStr | Synthesis of New Tricyclic 1,2-Thiazine Derivatives with Anti-Inflammatory Activity |
| title_full_unstemmed | Synthesis of New Tricyclic 1,2-Thiazine Derivatives with Anti-Inflammatory Activity |
| title_short | Synthesis of New Tricyclic 1,2-Thiazine Derivatives with Anti-Inflammatory Activity |
| title_sort | synthesis of new tricyclic 1 2 thiazine derivatives with anti inflammatory activity |
| topic | synthesis tricyclic compounds 1,2-thiazine cyclooxygenase inhibition model membrane DSC |
| url | https://www.mdpi.com/1422-0067/22/15/7818 |
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