Antioxidant action of 3-mercapto-5H-1,2,4-triazino[5,6-b]indole-5-acetic acid, an efficient aldose reductase inhibitor, in a 1,1′-diphenyl-2-picrylhydrazyl assay and in the cellular system of isolated erythrocytes exposed totert-butyl hydroperoxide

Prnová, Marta Šoltésová; Ballekova, Jana; Májeková, Magdaléna; Štefek, Milan

doi:10.1179/1351000215y.0000000019

Cited by 13 publications

(9 citation statements)

References 45 publications

(51 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Scheme 1 , the reaction steps from (c) to (d) and from (e) to (f). The later observation is supported also by results of Šoltésová Prnová et al [ 26 ].…”

Section: Resultssupporting

confidence: 80%

Oxidative Degradation of High-Molar-Mass Hyaluronan: Effects of Some Indole Derivatives to Hyaluronan Decay

Valachová

Mach

Šoltés

2020

IJMS

View full text Add to dashboard Cite

Indole derivatives such as isatin (a natural compound), cemtirestat, stobadine, and its derivatives (synthetic compounds) are known to have numerous positive effects on human health due to regulation of oxidative status. The aim of the study was to assess radical scavenging capacities of these compounds and explore their potential protective effects against reactive oxygen species formed during Cu(II) ions and ascorbate-induced degradation of high-molar-mass hyaluronan. Based on the IC50 values determined by the ABTS assay, the most effective compound was SM1M3EC2·HCl reaching the value ≈ 11 µmol/L. The lowest IC50 value reached in the DPPH assay was reported for cemtirestat ≈ 3 µmol/L. Great potency of inhibition of hyaluronan degradation was shown by cemtirestat, followed by isatin even at low concentration 10 µmol/L. On the other hand, stobadine·2HCl had also a protective effect on hyaluronan degradation, however at greater concentrations compared to cemtirestat or isatin. SME1i-ProC2·HCl reported to be a less effective compound and SM1M3EC2·HCl can be considered almost ineffective compared to stobadine·2HCl. In conclusion, our results showed that both isatin and cemtirestat were capable of attenuating the degradation of high-molar-mass hyaluronan due to their ability to complex/sequester cupric ions.

show abstract

“…Scheme 1 , the reaction steps from (c) to (d) and from (e) to (f). The later observation is supported also by results of Šoltésová Prnová et al [ 26 ].…”

Section: Resultssupporting

confidence: 80%

Oxidative Degradation of High-Molar-Mass Hyaluronan: Effects of Some Indole Derivatives to Hyaluronan Decay

Valachová

Mach

Šoltés

2020

IJMS

View full text Add to dashboard Cite

show abstract

“…In the series 5 , the antiradical activity of the most efficient AR inhibitor cemtirestat ( 5a ) markedly exceeded that of equimolar melatonin ( Table 10 ). On placing an isopropyl group on the S atom resulting in compound 5f , thus preventing thione–thiol tautomerism and deprotonation of the –SH group, the antiradical activity of compound 5f was completely lost [ 87 ].…”

Section: Studies At the Level Of Isolated Enzymes And Free Radical Models In Vitro And In Silico: Sarmentioning

confidence: 99%

“…The total stoichiometry of DPPH scavenging by cemtirestat ( 5a ) was determined. Under the experimental conditions used, one molecule of compound 5a was found to quench about 1.5 DPPH radicals [ 87 ].…”

Section: Studies At the Level Of Isolated Enzymes And Free Radical Models In Vitro And In Silico: Sarmentioning

confidence: 99%

“…In the presence of compound 5a , the lag period increased significantly in a concentration-dependent manner. At 1 mM concentration of compound 5a , no hemolysis occurred during the 3-h incubation period [ 87 ]. Based on lag phase prolongation, it can be deduced that the erythrocytes were protected by compound 5a against t -BuOOH-induced hemolysis.…”

Section: Biological Activity In the Rat Models Of Oxidative Stress And Diabetic Complicationsmentioning

confidence: 99%

“…Among the novel derivatives, compound 5a was patented (P3). At the present time, it is in the stage of complex preclinical evaluation under the name of cemtirestat [ 76 , 78 , 87 , 88 , 89 , 94 , 95 , 96 , 97 , 98 , 99 , 100 ]. Apparently, there are several advantages of cemtirestat over the clinically used epalrestat, namely lower molecular weight, better water solubility, higher AR inhibition activity recorded both at the level of isolated enzyme ( Table 2 and Table 4 ) and at the organ level of isolated rat eye lenses ( Table 13 ) and additional AO action ( Table 10 and Table 11 , Figure 15 and Figure 16 ).…”

Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

See 2 more Smart Citations

Development of Novel Indole-Based Bifunctional Aldose Reductase Inhibitors/Antioxidants as Promising Drugs for the Treatment of Diabetic Complications

et al. 2021

Self Cite

View full text Add to dashboard Cite

Aldose reductase (AR, ALR2), the first enzyme of the polyol pathway, is implicated in the pathophysiology of diabetic complications. Aldose reductase inhibitors (ARIs) thus present a promising therapeutic approach to treat a wide array of diabetic complications. Moreover, a therapeutic potential of ARIs in the treatment of chronic inflammation-related pathologies and several genetic metabolic disorders has been recently indicated. Substituted indoles are an interesting group of compounds with a plethora of biological activities. This article reviews a series of indole-based bifunctional aldose reductase inhibitors/antioxidants (ARIs/AOs) developed during recent years. Experimental results obtained in in vitro, ex vivo, and in vivo models of diabetic complications are presented. Structure–activity relationships with respect to carboxymethyl pharmacophore regioisomerization and core scaffold modification are discussed along with the criteria of ‘drug-likeness”. Novel promising structures of putative multifunctional ARIs/AOs are designed.

show abstract

Design of Improved Antidiabetic Drugs: A Journey from Single to Multitarget Agents

2022

View full text Add to dashboard Cite

Multifactorial diseases exhibit a complex pathophysiology with several factors contributing to their pathogenesis and development. Examples of such disorders are neurodegenerative (e. g. Alzheimer's, Parkinson's) and cardiovascular diseases (e. g. atherosclerosis, metabolic syndrome, diabetes II). Traditional therapeutic approaches with single‐target drugs have been proven, in many cases, unsatisfactory for the treatment of multifactorial diseases such as diabetes II. The well‐established by now strategy of multitarget drugs is constantly gaining interest and momentum, as a more effective approach. The development of pharmacomolecules able to simultaneously modulate multiple relevant‐to‐the‐disease targets has already several successful examples in various fields and has, as such, inspired the design of multitarget antidiabetic agents; this review highlights the design aspect and efficacy of this approach for improved antidiabetics by presenting several examples of successful pharmacophore combinations in (multitarget) agents that modulate two or more molecular targets involved in diabetes II, resulting in a superior antihyperglycemic profile.

show abstract

Antioxidant action of 3-mercapto-5H-1,2,4-triazino[5,6-b]indole-5-acetic acid, an efficient aldose reductase inhibitor, in a 1,1′-diphenyl-2-picrylhydrazyl assay and in the cellular system of isolated erythrocytes exposed totert-butyl hydroperoxide

Cited by 13 publications

References 45 publications

Oxidative Degradation of High-Molar-Mass Hyaluronan: Effects of Some Indole Derivatives to Hyaluronan Decay

Oxidative Degradation of High-Molar-Mass Hyaluronan: Effects of Some Indole Derivatives to Hyaluronan Decay

Development of Novel Indole-Based Bifunctional Aldose Reductase Inhibitors/Antioxidants as Promising Drugs for the Treatment of Diabetic Complications

Design of Improved Antidiabetic Drugs: A Journey from Single to Multitarget Agents

Contact Info

Product

Resources

About