1-4-benzothiazine has been researched along with Atherosclerosis* in 2 studies
1 review(s) available for 1-4-benzothiazine and Atherosclerosis
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Balancing Antioxidant, Hypolipidemic and Anti-inflammatory Activity in a Single Agent: The Example of 2-Hydroxy-2-Substituted Morpholine, 1,4-Benzoxazine and 1,4-Benzothiazine Derivatives as a Rational Therapeutic Approach against Atherosclerosis.
In line with our previous studies, novel morpholine and benzoxa(or thia)zine lead compounds have been developed through a rational design that modulate a multiplicity of targets against atherosclerosis. We have evaluated the most promising compounds for their efficiency to a) intercept and scavenge free radicals, b) inhibit the metal ion (Cu2+)- induced LDL oxidation c) act intracellularly as antioxidants in THP-1 monocytes from a leukemic patient and d) inhibit the pro-inflammatory enzymes cyclooxygenase-1 (COX-1) and -2 (COX-2) in vitro. Furthermore, two representative compounds were tested for their potential to decrease lipidemic parameters (TC, LDL and TG) in hyperlipidemic mice. Most derivatives indicated a remarkable antioxidant activity, while at the same time exhibited a significant in vitro anti-inflammatory activity, inhibiting COX-1 or/and COX-2 activity at 20 μΜ. In addition, after their long-term administration, compounds 6 and 8 afforded considerable activity in a chronic experimental animal model of hyperlipidemia (after high fat diet administration). The multifunctional pharmacological profile exhibited by the compounds of this study renders them interesting lead compounds for the development of novel agents against atherosclerosis. Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Antioxidants; Atherosclerosis; Benzoxazines; Humans; Hypolipidemic Agents; Molecular Structure; Morpholines; Thiazines | 2017 |
1 other study(ies) available for 1-4-benzothiazine and Atherosclerosis
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Developing potential agents against atherosclerosis: Design, synthesis and pharmacological evaluation of novel dual inhibitors of oxidative stress and Squalene Synthase activity.
For the treatment of multifactorial and complex diseases, it has become increasingly apparent that compounds acting at multiple targets often deliver superior efficacy compared to compounds with high specificity for only a single target. Based on previous studies demonstrating the important antioxidant and anti-hyperlipidemic effect of morpholine and 1,4-benzo(x/thi)azine derivatives (A-E), we hereby present the design, synthesis and pharmacological evaluation of novel dual-acting molecules as a therapeutic approach for atherosclerosis. Analogues 1-10 were rationally designed through structural modifications of their parent compounds (A-E) in order for structure-activity relationship studies to be carried out. Most compounds showed a significant inhibition against Squalene Synthase activity exhibiting at the same time a very potent multimodal antioxidant (against lipid peroxidation and as free-radical scavengers) effect, thus bringing to light the 2-aryl-1,4-benzo(x/thia)zin-2-ol scaffold as an outstanding pharmacophore for the design of potent antioxidants. Finally, the replacement of the octahydro-1,4-benzoxazine moiety of lead compound D with its respective 1,4-benzothiazine (compound 4), although conserved (anti-hypercholesterolemic) or even improved (anti-hyperlipidemic) activity, did not preserve the anti-diabetic effect of D. Topics: Animals; Atherosclerosis; Cyclooxygenase 1; Cyclooxygenase 2; Diabetes Mellitus, Type 2; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Design; Enzyme Inhibitors; Farnesyl-Diphosphate Farnesyltransferase; Humans; Hypolipidemic Agents; Male; Mice; Mice, Hairless; Molecular Structure; Morpholines; Oxidative Stress; Rats; Structure-Activity Relationship; Thiazines | 2017 |