(2-Benzyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indol-8-yl)-acetic acid: An aldose reductase inhibitor and antioxidant of zwitterionic nature

Štefek, Milan; Tsantili‐Kakoulidou, Anna; Milackova, Ivana; Juskova, Maria; Snirc, Vladimir; Triantos, Nikos

doi:10.1016/j.bmc.2011.09.053

Cited by 9 publications

(3 citation statements)

References 14 publications

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“…The presence of a positive charge on the tertiary nitrogen, which predisposes these compounds to form double-charged zwitterionic species, has apparently a detrimental effect on AR inhibition efficacy. Similarly, only modest AR inhibition was recorded for structurally related zwitterionic 8-carboxymethylated pyridoindoles [ 63 , 72 ].…”

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

confidence: 99%

“…The pH-lipophilicity profile experimentally determined for compounds 2c and 2d in the system of 1-octanol/buffer was characterized by a bell-shaped curve, with a maximal distribution ratio near neutral pH ( Figure 14 ) [ 63 ]. The presence of zwitterions was experimentally proved [ 72 ].…”

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

confidence: 99%

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

et al. 2021

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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.

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

confidence: 99%

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

confidence: 99%

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

et al. 2021

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“…A number of the most important drug structures have been identified by analyzing the results of experimental bioscreening of a large set of substances, their medical applications and structural data (Rekker and Mannhold, 1992). Among them are pyrido[4,3-b]indole derivatives with a wide range of biological activity: antihistamine, central depressant, anti-inflammatory, neuroleptic and other types (Ivachtchenko et al, 2010, Stefek et al, 2011, Dondas et al, 2016). The structural analogues of this series, and the antihistamine drug Dimebon (Latrepirdine) in particular, were found to slow down the neurodegenerative process (Ikonomidou and Turski, 2002, Doody et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

New derivatives of hydrogenated pyrido[4,3-b]indoles as potential neuroprotectors: Synthesis, biological testing and solubility in pharmaceutically relevant solvents

Blokhina

Sharapova

Ol’khovich

et al. 2018

Saudi Pharmaceutical Journal

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The derivatives of hydrogenated pyrido[4,3-b]indoles as potential neuroprotectors have been synthesized. The different substituents were introduced into position 8 of the carboline fragment of the molecule: methyl-, methoxy-, fluorine- and chlorine-. Biological tests have shown that all the studied compounds can modulate glutamate-dependent uptake of calcium ions in rats' cerebral cortex synaptosomes. The shake-flask method was used to measure the solubility of the compounds in the buffer solution (pH 7.4), hexane and 1-octanol within the temperature interval of 293.15-313.15 К. All the derivatives have been found to have low solubility (not exceeding 8 ∙ 10 mole fractions) in the mentioned solvents. The effect of thermophysical and protolytic properties of the compounds on the solubility have been studied and the thermodynamic functions of compounds dissolution in the solvents used have been calculated.

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Indoles

Chadha

Silakari

2018

Key Heterocycle Cores for Designing Multitargeting Molecules

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(2-Benzyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indol-8-yl)-acetic acid: An aldose reductase inhibitor and antioxidant of zwitterionic nature

Cited by 9 publications

References 14 publications

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

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

New derivatives of hydrogenated pyrido[4,3-b]indoles as potential neuroprotectors: Synthesis, biological testing and solubility in pharmaceutically relevant solvents

Indoles

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