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Article

Synthesis of New Tricyclic 1,2-Thiazine Derivatives with Anti-Inflammatory Activity

1
Department of Medicinal Chemistry, Faculty of Pharmacy, Wroclaw Medical University, Borowska 211, 50-556 Wrocław, Poland
2
Department of Pharmacology, Faculty of Medicine, Wroclaw Medical University, J. Mikulicza-Radeckiego 2, 50-345 Wrocław, Poland
3
Department of Inorganic Chemistry, Faculty of Pharmacy, Wroclaw Medical University, Borowska 211a, 50-556 Wrocław, Poland
*
Author to whom correspondence should be addressed.
Academic Editors: Andrea Spallarossa and Eleonora Russo
Int. J. Mol. Sci. 2021, 22(15), 7818; https://doi.org/10.3390/ijms22157818
Received: 10 June 2021 / Revised: 16 July 2021 / Accepted: 19 July 2021 / Published: 22 July 2021
(This article belongs to the Special Issue Drug Design, Synthesis and Delivery)
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. View Full-Text
Keywords: synthesis; tricyclic compounds; 1,2-thiazine; cyclooxygenase inhibition; model membrane; DSC; molecular docking synthesis; tricyclic compounds; 1,2-thiazine; cyclooxygenase inhibition; model membrane; DSC; molecular docking
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MDPI and ACS Style

Maniewska, J.; Wiatrak, B.; Czyżnikowska, Ż.; Szczęśniak-Sięga, B.M. Synthesis of New Tricyclic 1,2-Thiazine Derivatives with Anti-Inflammatory Activity. Int. J. Mol. Sci. 2021, 22, 7818. https://doi.org/10.3390/ijms22157818

AMA Style

Maniewska J, Wiatrak B, Czyżnikowska Ż, Szczęśniak-Sięga BM. Synthesis of New Tricyclic 1,2-Thiazine Derivatives with Anti-Inflammatory Activity. International Journal of Molecular Sciences. 2021; 22(15):7818. https://doi.org/10.3390/ijms22157818

Chicago/Turabian Style

Maniewska, Jadwiga, Benita Wiatrak, Żaneta Czyżnikowska, and Berenika M. Szczęśniak-Sięga. 2021. "Synthesis of New Tricyclic 1,2-Thiazine Derivatives with Anti-Inflammatory Activity" International Journal of Molecular Sciences 22, no. 15: 7818. https://doi.org/10.3390/ijms22157818

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