Antioxidant properties of 2,5-substituted 6H-1,3,4-thiadiazines promising for experimental therapy of diabetes mellitus

Gerasimova, E. L.; Gazizullina, E. G.; Igdisanova, Dinara; Sidorova, L. P.; Цейтлер, Т. А.; Емельянов, В. В.; Чупахин, О. Н.; Иванова, А. В.

doi:10.1007/s11172-022-3702-0

Cited by 3 publications

(3 citation statements)

References 34 publications

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“…The patterns are consistent with the literature data on the relatively low rates of the reaction of α-tocopherol with free radicals in aqueous media and the structural features of the interaction of sterically hindered phenols with radicals [ 26 , 27 ]. In addition, dependences of this type were registered for synthesized compounds used in the treatment of various diseases: derivatives of 6H-1,3,4-thiadiazines—newly synthesized compounds, promising antidiabetic drugs with pleiotropic activity (antioxidant and antiglycation) [ 22 ], which have a prolonged activity, and for compounds of the azoloazine series modified with polyphenolic antioxidant fragments that exhibit antiviral and antioxidant activity [ 21 ]. Figure 5 shows the kinetic dependences of the potential for thiadiazine (1AZ) and azoloazine (1TH) derivatives.…”

Section: Resultsmentioning

confidence: 99%

“…Thiadiazines are capable of transformation into substituted mercaptopyrazoles [ 31 ], which react with potassium hexacyanoferrate (III). At the same time, the rate of this transformation is low and, accordingly, the rate of the reaction with potassium hexacyanoferrate (III) is low for the thiadiazine derivatives [ 22 ]. This does not allow the correct determination of the residual concentration of thiadiazines in conditions of competing kinetics: the initiation of a radical reaction and the reaction of thiadiazines in potassium hexacyanoferrate (III).…”

Section: Resultsmentioning

confidence: 99%

“…The objects of the research were solutions of antioxidants of natural and synthetic origin: ascorbic acid, uric acid, glutathione, cysteine, catechol, gallic acid, chlorogenic acid, caffeic acid, α-tocopherol, 2,6-ditretbutylphenol, 2,6-ditretbutyl-4-methylphenol (ionol), and compounds of the azoloazine series modified with polyphenol antioxidant fragments ( Figure 1 ), as promising molecules for the creation of “double” action drugs [ 21 ]; derivatives of 6H-1,3,4-thiadiazines are newly synthesized compounds ( Figure 2 ), promising antidiabetic drugs with pleiotropic activity [ 22 ].…”

Section: Methodsmentioning

confidence: 99%

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Kinetic Potentiometry as a Method for Studying the Interactions of Antioxidants with Peroxyl Radicals

Gerasimova,

Salimgareeva,

Magasumova

et al. 2023

Antioxidants

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This work presents a new method using kinetic potentiometry to study the thermodynamic and kinetic parameters of the reactions of antioxidants with peroxyl radicals. The rate constants of the reaction of antioxidants with radicals have been determined, and the groups of “fast” and “slow” antioxidants have been conventionally distinguished. Fast antioxidants include ascorbic, uric, gallic, chlorogenic, caffeic acids, glutathione, L-cysteine, and catechol with constant values from (1.05–9.25) × 103 M·s−1; “slow” antioxidants are α-tocopherol (in aqueous media), ionol, 2,6-ditretbutylphenol, and compounds of the azoloazine series, modified with polyphenolic fragments, with constant values from (4.00–8.50) × 102 M·s−1. It is shown that the value of the rate constant is directly related to the type of kinetic dependence of the potential recorded when an antioxidant is introduced into the solution of the radical initiator. It is shown that the method with the determination of the induction period is difficult in the study of “slow” antioxidants. It has been established that the area above the curve of the kinetic dependence Exp(∆E) is directly related to the amount of inhibited peroxyl radicals and can be used to assess the inhibitory properties of an antioxidant from a thermodynamic point of view. “Fixed time method” and “Initial rate method” were used. Positive correlations between the described method have been established. The utility of the parameter of the area above the curve of the kinetic dependence Exp(∆E) in the study of objects of complex composition is shown.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Kinetic Potentiometry as a Method for Studying the Interactions of Antioxidants with Peroxyl Radicals

Gerasimova,

Salimgareeva,

Magasumova

et al. 2023

Antioxidants

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An activation-based high throughput screen identifies caspase-10 inhibitors

Castellón,

Yuen,

Han

et al. 2024

Preprint

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Caspases are a family of highly homologous cysteine proteases that play critical roles in inflammation and apoptosis. Small molecule inhibitors are useful tools for studying caspase biology, complementary to genetic approaches. However, achieving inhibitor selectivity for individual members of this highly homologous enzyme family remains a major challenge in developing such tool compounds. Prior studies have revealed that one strategy to tackle this selectivity gap is to target the precursor or zymogen forms of individual caspases, which share reduced structural homology when compared to active proteases. To establish a screening assay that favors the discovery of zymogen-directed caspase-10 selective inhibitors, we engineered a low-background and high-activitytobacco etchvirus (TEV)--activated caspase-10 protein. We then subjected this turn-on protease to a high-throughput screen of approximately 100,000 compounds, with an average Z’ value of 0.58 across all plates analyzed. Counter screening, including against TEV protease, delineated bona fide procaspase-10 inhibitors. Confirmatory studies identified a class of low-pH activatable caspase-10 inhibitors. In parallel, mode-of-action studies revealed that pifithrin-µ (PFTµ), a reported TP53 inhibitor, also functions as a promiscuous caspase inhibitor. Both inhibitor classes showed preferential zymogen inhibition. Given the generalized utility of activation assays, we expect our screening platform to have widespread applications in identifying state-specific protease inhibitors.

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Optimal strategy of new 6H-1,3,4-thiadiazines synthesis in search of the promising antidiabetic agents

Tseitler,

Sidorova,

Ivanova

et al. 2024

Chim.Tech.Acta

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In this work, we report a convenient method for the preparation of new 2-hydroxyethylamino-substituted 6Н-1,3,4-thiadiazine hydrobromides for the search of new agents with pleiotropic (antioxidant and antiglycating) activity. The synthesis is based on the cyclocondensation reaction of 4-substituted thiosemicarbazide with various α-haloketones. We compared approaches to the key intermediate for the synthesis of the 6H-1,3,4-thiadiazine system – 4-substituted thiosemicarbazide. The approach we proposed was modified to obtain the intermediate and is based on the reaction of a substituted carbamothioylthioacetate with hydrazine. This approach has a number of advantages, like fewer stages, atom economy, elimination of stages with the isolation of undesirable by-products, availability of starting materials and simplicity of the procedure. New 2-hydroxyethylamino-5-substituted 6H-1,3,4-thiadiazine hydrobromides were characterized by ¹H NMR, ¹³C NMR and elemental analysis.

show abstract

Antioxidant properties of 2,5-substituted 6H-1,3,4-thiadiazines promising for experimental therapy of diabetes mellitus

Cited by 3 publications

References 34 publications

Kinetic Potentiometry as a Method for Studying the Interactions of Antioxidants with Peroxyl Radicals

Kinetic Potentiometry as a Method for Studying the Interactions of Antioxidants with Peroxyl Radicals

An activation-based high throughput screen identifies caspase-10 inhibitors

Optimal strategy of new 6H-1,3,4-thiadiazines synthesis in search of the promising antidiabetic agents

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