11β-Hydroxysteroid Dehydrogenase Type 1 as a Potential Treatment Target in Cardiovascular Diseases

Kupczyk, Daria; Studzińska, Renata; Kołodziejska, Renata; Baumgart, Szymon; Modrzejewska, Martyna; Woźniak, Alina

doi:10.3390/jcm11206190

Cited by 4 publications

(2 citation statements)

References 155 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The inhibition of the activity of 11β-hydroxysteroid dehydrogenase type 1 reduces the level of cortisol, and thus reduces the mass of adipose tissue, insulin resistance, and central obesity, as well as lowers the level of total cholesterol. Selective inhibitors have significant potential as a pharmacological treatment for type 2 diabetes, obesity, and cardiovascular disease [20,21].…”

Section: Introductionmentioning

confidence: 99%

Lipophilic Studies and In Silico ADME Profiling of Biologically Active 2-Aminothiazol-4(5H)-one Derivatives

Redka,

Baumgart,

Kupczyk

et al. 2023

IJMS

Self Cite

View full text Add to dashboard Cite

Pseudothiohydantoin derivatives have a wide range of biological activities and are widely used in the development of new pharmaceuticals. Lipophilicity is a basic, but very important parameter in the design of potential drugs, as it determines solubility in lipids, nonpolar solvents, and makes it possible to predict the ADME profile. The aim of this study was to evaluate the lipophilicity of 28 pseudothiohydantoin derivatives showing the inhibition of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) using chromatographic methods. Experimentally, lipophilicity was determined by reverse phase thin layer chromatography (RP-TLC) and reverse phase high-performance liquid chromatography (RP-HPLC). In both methods, methanol was used as the organic modifier of the mobile phase. For each 2-aminothiazol-4(5H)-one derivative, a relationship was observed between the structure of the compound and the values of the lipophilicity parameters (log kw, RM0). Experimental lipophilicity values were compared with computer calculated partition coefficient (logP) values. A total of 27 of the 28 tested compounds had a lipophilicity value < 5, which therefore met the condition of Lipinski’s rule. In addition, the in silico ADME assay showed favorable absorption, distribution, metabolism, and excretion parameters for most of the pseudothiohydantoin derivatives tested. The study of lipophilicity and the ADME analysis indicate that the tested compounds are good potential drug candidates.

show abstract

Section: Introductionmentioning

confidence: 99%

Lipophilic Studies and In Silico ADME Profiling of Biologically Active 2-Aminothiazol-4(5H)-one Derivatives

Redka,

Baumgart,

Kupczyk

et al. 2023

IJMS

Self Cite

View full text Add to dashboard Cite

show abstract

“…Pseudothiohydantoin derivatives exhibit a number of biological activities, including antibacterial [ 1 , 2 , 3 , 4 ], antifungal [ 3 , 5 ], and antiviral [ 6 , 7 ]. They are also an interesting and promising class of compounds in the search for selective 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) inhibitors [ 8 ]. 11β-hydroxysteroid dehydrogenase belongs to the short-chain family of nicotinamide adenine dinucleotide (NAD) or nicotinamide adenine dinucleotide phosphate-dependent (NADP-dependent) dehydrogenases/reductases (SDRs).…”

Section: Introductionmentioning

confidence: 99%

Synthesis of Novel 2-(Cyclopentylamino)thiazol-4(5H)-one Derivatives with Potential Anticancer, Antioxidant, and 11β-HSD Inhibitory Activities

Baumgart

Kupczyk

Archała

et al. 2023

IJMS

Self Cite

View full text Add to dashboard Cite

In this study, a series of nine new 2-(cyclopentylamino)thiazol-4(5H)-one derivatives were synthesized, and their anticancer, antioxidant, and 11β-hydroxysteroid dehydrogenase (11β-HSD) inhibitory activities were tested. Anticancer activity has been assessed using the MTS (MTS: 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) assay against human colon carcinoma (Caco-2), human pancreatic carcinoma (PANC-1), glioma (U-118 MG), human breast carcinoma (MDA-MB-231), and skin melanoma (SK-MEL-30) cancer cell lines. Cell viability reductions, especially in the case of Caco-2, MDA-MB-231, and SK-MEL-30 lines, were observed for most compounds. In addition, the redox status was investigated and oxidative, but nitrosative stress was not noted at a concentration of 500 µM compounds tested. At the same time, a low level of reduced glutathione was observed in all cell lines when treated with compound 3g (5-(4-bromophenyl)-2-(cyclopentylamino)thiazol-4(5H)-one) that most inhibited tumor cell proliferation. However, the most interesting results were obtained in the study of inhibitory activity towards two 11β-HSD isoforms. Many compounds at a concentration of 10 µM showed significant inhibitory activity against 11β-HSD1 (11β-hydroxysteroid dehydrogenase type 1). The compound 3h (2-(cyclopentylamino)-1-thia-3-azaspiro[4.5]dec-2-en-4-one) showed the strongest 11β-HSD1 inhibitory effect (IC50 = 0.07 µM) and was more selective than carbenoxolone. Therefore, it was selected as a candidate for further research.

show abstract

Ag(i)-catalyzed asymmetric (2+4) annulation reaction of 5-alkenyl thiazolones: synthesis of enantioenriched spiro[cyclohexenamines-thiazolones]

Choudhary,

Deshpande,

Singh

2024

Chem. Commun.

View full text Add to dashboard Cite

show abstract

11β-Hydroxysteroid Dehydrogenase Type 1 as a Potential Treatment Target in Cardiovascular Diseases

Cited by 4 publications

References 155 publications

Lipophilic Studies and In Silico ADME Profiling of Biologically Active 2-Aminothiazol-4(5H)-one Derivatives

Lipophilic Studies and In Silico ADME Profiling of Biologically Active 2-Aminothiazol-4(5H)-one Derivatives

Synthesis of Novel 2-(Cyclopentylamino)thiazol-4(5H)-one Derivatives with Potential Anticancer, Antioxidant, and 11β-HSD Inhibitory Activities

Ag(i)-catalyzed asymmetric (2+4) annulation reaction of 5-alkenyl thiazolones: synthesis of enantioenriched spiro[cyclohexenamines-thiazolones]

Contact Info

Product

Resources

About