The Effects of Long-Term, Low- and High-Dose Beta-Carotene Treatment in Zucker Diabetic Fatty Rats: the Role of HO-1

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Synthesis, in Vitro Biological Evaluation, and Oxidative Transformation of New Flavonol Derivatives: The Possible Role of the Phenyl-N,N-Dimethylamino Group

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A NEW, VASOACTIVE HYBRID ASPIRIN CONTAINING NITROGEN MONOXIDE-RELEASING MOLSIDOMINE MOIETY

Ischemic heart conditions are among the main causes of sudden cardiac death worldwide. One of the strategies for avoiding myocardial infarction is the low-dose, prophylactic use of acetylsalicylic acid (ASA), an inhibitor of platelet aggregation. To avoid the gastrointestinal damage, ASA prodrugs bearing nitric oxide (NO)-donating moiety covalently conjugated to ASA have been synthesized and evaluated extensively worldwide. Herein the synthesis of a new hybrid ASA ester covalently attached to the NO donor linsidomine, an active metabolite of molsidomine (MOL) is reported. Cell viability assay and hemolysis tests were performed in H9c2 cells and rat erythrocytes, respectively. Our new compound, the ERJ-500 not affected negatively the viability of living cells in the concentration range of 100 nM to 100 µM. Using the ex vivo Langendorff method on hearts originated from female rats, compound ERJ-500 displayed a dose-dependent, outwashable vasodilative effect in coronary arteries. Vasodilation was observed on isolated working heart model as well, with elevated stroke volume in hearts treated with ERJ-500. Furthermore, a decreased infarct size was also noticed in ERJ-500 treated hearts after ischemia/reperfusion. Based on these observations it can be expected that our new hybrid ASA may contribute to new pharmacological tool in the therapy of ischemic heart conditions and associated syndromes

Dataset on structure, stability and myocardial effects of a new hybrid aspirin containing nitrogen monoxide-releasing molsidomine moiety

Herein 1H and 13C NMR spectra of ERJ-500, a new hybrid aspirin derivative, covalently conjugated to nitrogen monoxide donor linsidomine are presented as well as NMR spectra of its synthetic intermediate compounds. HPLC-MS measurements data are also included, demonstrating the stability of the linsidomine-aspirin hybrid in oxidation reactions. This data article also concerns miscellaneous myocardial parameters of isolated rat hearts as a complementation of the tables shown in the paper entitled “A new, vasoactive hybrid aspirin containing nitrogen monoxidereleasing molsidomine moiety” Szoke et al., 2019. Column tables represent data of aorta flow, aortic pressure, derivated aortic pressure and cardiac output

Flavonoid származékok in vitro antioxidáns tulajdonságainak, citotoxicitásának és oxidatív transzformációjának vizsgálata

A kutatás első részében kilenc flavonoid származék antioxidáns hatását és citotoxicitását tanulmányoztuk. Eredményeinkből kiderült, hogy a 4-N,N-dimetilamino flavon (vegyület 865) (24. ábra) jelentős antioxidáns és citoprotektív hatással rendelkezik, valamint metabolikusan stabil. Ezen adatok alapján, hat új flavonol származékot terveztünk és állítottunk elő a kutatás második részében, amely során vizsgáltuk a fenil-N,N-dimetilamino-csoport hatását az antioxidáns aktivitásra. Az eredmények azt mutatták, hogy a fenil-N,N-dimetilamin-csoportot tartalmazó molekulák (6a, 6c és 6e) (25. ábra) antioxidáns aktivitása nagyobb, továbbá cardioprotektív hatással is rendelkeznek H9c2 sejtvonal esetében. A kutatás első és második részének az összevont eredményei szerint a fenil-N,N-dimetilamino-csoportnak kulcsszerepe van a flavonoidok antioxidáns aktivitásában csoportnak kulcsszerepe van a flavonoidok antioxidáns aktivitásában és citotoxicitásában egyaránt. A oxidatív stabilitása ígéretes jelöltekké teszi a 865 és 6c molekulákat az oxidatív stresszel kapcsolatos betegségek vizsgálatában a megfelelő állatmodelleket alkalmazva. In Study I, nine flavonoids were tested for their possible antioxidant and cytotoxic activities. As the result of this investigation the significant antioxidant potency, cytoprotective activity, and the metabolic stability of 4-N,N-dimethylamino-flavon (compound 865) (Figure 23) were observed. Based on this outcome, six new flavonols were designed and synthetized for Study II, in which we investigated the effect of phenyl-N,N-dimethylamino group on the antioxidant activity. The N,N-dimethylamino group containing flavonol derivatives (6a, 6c and 6e) (Figure 24) showed increased activity during different antioxidant assays, and the also exhibited cytoprotective effect on H9c2 cardiomyoblast cells. The results of both Study I and Study II suggest that the phenyl-N,N-dimethylamino group has a crucial role in the antioxidant potency and in the cytotoxicity of flavonoid derivatives. The oxidative stability of 865 and 6c also makes them an ideal candidate for the investigation of oxidative stress related diseases in suitable animal models.N

Synthesis, in Vitro Biological Evaluation, and Oxidative Transformation of New Flavonol Derivatives: The Possible Role of the Phenyl-N,N-Dimethylamino Group

Six new flavonols (6a–f) were synthesized with Claisen–Schmidt and Suzuki reactions and they were fully characterized by spectroscopic methods. In order to evaluate their antioxidant activities, their oxygen radical absorption capacity and ferric reducing antioxidant power were measured, along with their free radical scavenging activity against 2,20 -azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) and 2,2-diphenyl-1-picrylhydrazylradicals. In addition, their cytotoxicity on H9c2 cardiomyoblast cells was also assessed by a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Compounds bearing the phenyl-N,N-dimethylamino group (6a, 6c, and 6e) exhibited promising antioxidant potency and did not have any cytotoxic effect. After a consideration of these data, the oxidative transformation of the 6c compound was investigated in vitro with a chemical Fenton reaction and the identification of the formed oxidation products was performed by mass spectrometry. Two potential metabolites were detected. Based on these results, compound 6c can be a model compound for future developments. Overall, this work has proved the involvement of the phenyl-N,N-dimethylamino group in the antioxidant activity of flavonols