Structural aspects of flavonoids as trypsin inhibitors

Maliar, Tibor; Jedinák, Andrej; Kadrabová, J; Šturdı́k, Ernest

doi:10.1016/j.ejmech.2003.12.003

Cited by 74 publications

(60 citation statements)

References 16 publications

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“…In fact, compounds were tested as perspective building blocks of potential anticancer agents taking into account the size of the molecules. The flavonoid quercetin was used as a standard for all tested proteases (Maliar et al, 2004;Mantle et al, 1999).…”

Section: Resultsmentioning

confidence: 99%

“…One of the possibilities of cancer treatment is to suppress the activity of proteases (mainly urokinase, cathepsins, and metalloproteinases) that play an important role in tumour invasion and metastasis (Jediná k and Maliar, 2005). Therefore, proteases present an attractive target in therapy and pharmaceutical research (Tossi et al, 2000;Maliar et al, 2004). A very perspective strategy how to control proteases seems to be the development of selective low-molecular weight inhibitors from natural sources with possible lower toxicity.…”

Section: Introductionmentioning

confidence: 99%

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Antiprotease and Antimetastatic Activity of Ursolic Acid Isolated from Salvia officinalis

Jedinák

Múčková²,

Kostálová

et al. 2006

Zeitschrift Für Naturforschung C

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Proteases play a regulatory role in a variety of pathologies including cancer, pancreatitis, thromboembolic disorders, viral infections and many others. One of the possible strategies how to combat with these pathologies seems to be the use of low molecular inhibitors. Natural products were evaluated in the in vitro antiprotease assay on serine proteases (trypsin, thrombin and urokinase) and on the cysteine protease cathepsin B. We found interesting results for -ursolic acid isolated from Salvia officinalis, which significantly inhibited all tested proteases in vitro in the micromolar range. -Ursolic acid showed the strongest inhibition activity to urokinase (IC 50 = 12 μm) and cathepsin B (IC 50 = 10 μm) as proteases included in tumour invasion and metastasis indicated possible anticancer effectivity. Therefore, we tested the ability of -ursolic acid at doses of 50, 75 and 100 mg/kg given i.p. to inhibit lung colonization of B16 mouse melanoma cells in vivo. We found, that -ursolic acid significantly decreased the number of B16 colonies in the lungs of mice at the dose 50 mg/kg (p Ͻ 0.05).

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Antiprotease and Antimetastatic Activity of Ursolic Acid Isolated from Salvia officinalis

Jedinák

Múčková²,

Kostálová

et al. 2006

Zeitschrift Für Naturforschung C

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“…Literature reviews showed that phenolics had a capacity to 2004 Maliar et al [28] concluded that flavonoids could be used as potential trypsin inhibitors due to their hydrophobic nature. They concluded that quercetin and apigenin were the most effective phenolics for the inhibition of trypsin enzyme activity [29].…”

Section: Phenolic Content Studiesmentioning

confidence: 99%

Kinetic and structural characterization of interaction between trypsin and Equisetum arvense extract

Uslu¹,

Bayraktar²,

Ceylan³

2014

Turk J Bioch

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Kinetic and structural characterization of interaction between trypsin and Equisetum arvense extract [Trypsin ve Equisetum arvense özütü arasındaki etkileşimin kinetik ve yapısal karakterizasyonu] ABSTRACT Objective: In this study the inhibitory effect of E. arvense extract on trypsin activity and the effect of trypsin on E. arvense extract were studied. In addition the nature of the interaction between the extract and trypsin was investigated. Methods: The inhibitory effect ethanol extract of E. arvense on trypsin activity was determined using trypsin enzyme assay. The structural effects of the extract-trypsin interaction for the extract were analyzed by FTIR. Finally, the HPLC analyses were carried out to analyze the individual components of the extract and the supernatant and soluble precipitate phases. Results: E. arvense extract was found to decrease total percent activity of trypsin to 5% in 24 hour at 24 °C. FTIR analyses indicated that the interaction between trypsin and E. arvense extract caused changes in the structure and hydrogen bonding behavior and composition of the extract proteins. These interactions also caused the extract lipids to accumulate in the insoluble precipitate phase. Most of the phenolics remained in the supernatant phase enhancing the inactivation of trypsin. However, the precipitated compounds were shown to be of apolar in nature as shown in the HPLC chromatograms. Conclusion:The methods that were used showed that the high phenolic content of E. arvense was the main reason for the inhibition of trypsin enzyme activity by denaturing the enzyme. of 1:20. The dry leafs particles were shaked in the solution for overnight at 300 rpm at 24 °C. After the centrifugation at 2000xg for 5 minutes the supernatant was collected into 50 ml falcon tubes. The alcohol in the liquid phase was evaporated with a rotary evaporator. The aqueous extract was frozen for 24 hours and then freeze dried in a lyophilizer (Telstar-Cryodos). Preparation of inhibition solutionE. arvense extract was dissolved in distilled water to a final concentration of 10 mg/ml. By serial dilutions of stock solution 2 mg/ml, 0.2 mg/ml and 0.02 mg/ml concentrations were prepared. Preparation of trypsin solutionBovine pancreatic trypsin was purchased from Fluka Analytical (cat.93610) and used without further purification. Lyophilized powder of bovine pancreatic trypsin (Fluka Analytical, USA) was dissolved in 1 mM HCl to a final concentration of 0.1 mg/ml. Determination of enzyme kineticsTrypsin catalyzes the hydrolysis of N-benzoyl-L-arginine ethyl ester (BAEE) to N-benzoyl-L-arginine (BA) and ethanol. The slope of the absorbance versus time graph was the production rate of BA at pH 7.6.The reaction was held in a total volume of 3.2 ml quartz cuvette at 25 °C. The unit of trypsin activity was previously determined as 1 µmol BA produced per minute at 253 nm, at pH 7.6 and 25 °C. The reaction was carried out in 100 mM Tris buffer solution. To determine absorption of blank solution, 3050 μl tris buffer and 150 μl of BAEE solution ...

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“…Flavanones have attracted much attention because they are physiologically active compounds with a wide range of biological activities, including free radical scavenging; stimulation of apoptosis; and inhibition of nitric oxide production, cell proliferation, aromatase activity and trypsin activity [24][25][26][27][28] . Recently, Cui et al reported that several flavanones isolated from the stem bark of Erythrina abyssinica (including prenylated flavanones, abyssinoflavanones and flavanones bearing a 2,2-dimethylpyrano ring) exhibited moderate inhibitory effects against PTP1B [29][30][31][32] .…”

Section: Introductionmentioning

confidence: 99%

Synthesis and characterization of 5,7-dihydroxyflavanone derivatives as novel protein tyrosine phosphatase 1B inhibitors

Sun

Gao

et al. 2012

Journal of Enzyme Inhibition and Medicinal Chemistry

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Structural aspects of flavonoids as trypsin inhibitors

Cited by 74 publications

References 16 publications

Antiprotease and Antimetastatic Activity of Ursolic Acid Isolated from Salvia officinalis

Antiprotease and Antimetastatic Activity of Ursolic Acid Isolated from Salvia officinalis

Kinetic and structural characterization of interaction between trypsin and Equisetum arvense extract

Synthesis and characterization of 5,7-dihydroxyflavanone derivatives as novel protein tyrosine phosphatase 1B inhibitors

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