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Anti-Inflammatory Properties of Novel 1,2-Benzothiazine Derivatives and Their Interaction with Phospholipid Model
Berenika M Szczęśniak-Sięga1, Jadwiga Maniewska1, Benita Wiatrak2
1Department of Medicinal Chemistry, Faculty of Pharmacy, Wroclaw Medical University, Borowska 211, 50-556 Wroclaw, Poland.
Abstract:
The design of novel anti-inflammatory drugs remains a critical area of research in the development of effective treatments for inflammatory diseases. In this study, a series of 1,2-benzothiazine was evaluated through a multifaceted approach. In particular, we investigated the potential interactions of the potential drugs with lipid bilayers, an important consideration for membrane permeability and overall pharmacokinetics. In addition, we evaluated their ability to inhibit cyclooxygenase 1 and cyclooxygenase 2 activity and selectivity using both a cyclooxygenase inhibition assay and molecular docking simulations. To evaluate their therapeutic potential, we performed in vitro assays to measure cytokine mRNA expression in inflamed cells. The antioxidant activity was evaluated using both in vitro assays, such as 2,2-diphenyl-1-picrylhydrazyl and 2,2-azino-bis-3-ethylbenzothiazoline-6-sulphonic acid scavenging, to determine the compounds' capacity to neutralize free radicals and reduce oxidative stress. Theoretical calculations, including density functional theory, were used to predict the reactivity profiles of the compounds.
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