The increasing resistance of pathogens to common antibiotics, as well as the need to control urease activity to improve the yield of soil nitrogen fertilization in agricultural applications, has stimulated the development of novel classes of molecules that target urease as an enzyme. In this context, the newly developed compounds on the basis of 1-heptanoyl-3-arylthiourea family were evaluated for Jack bean urease enzyme inhibition activity to validate their role as potent inhibitors of this enzyme. 1-Heptanoyl-3-arylthioureas were obtained in excellent yield and characterized through spectral and elemental analysis. All the compounds displayed remarkable potency against urease inhibition as compared to thiourea standard. It was found that novel compounds fulfill the criteria of drug-likeness by obeying Lipinski's rule of five. Particularly compound 4a and 4c can serve as lead molecules in 4D (drug designing discovery and development). Kinetic mechanism and molecular docking studies also carried out to delineate the mode of inhibition and binding affinity of the molecules.
- MeSH
- Canavalia enzymologie MeSH
- inhibitory enzymů chemie farmakologie MeSH
- kinetika MeSH
- molekulární struktura MeSH
- simulace molekulového dockingu * MeSH
- thiomočovina chemie farmakologie MeSH
- ureasa antagonisté a inhibitory metabolismus MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- vztahy mezi strukturou a aktivitou MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Hydrophobins are small proteins that play a role in a number of processes during the filamentous fungi growth and development. These proteins are characterized by the self-assembly of their molecules into an amphipathic membrane at hydrophilic-hydrophobic interfaces. Isolation and purification of hydrophobins generally present a challenge in their analysis. Hydrophobin SC3 from Schizophyllum commune was selected as a representative of class I hydrophobins in this work. A novel procedure for selective and effective isolation of hydrophobin SC3 based on solid-phase extraction with polytetrafluoroethylene microparticles loaded in a small self-made microcolumn is reported. The tailored binding of hydrophobins to polytetrafluoroethylene followed by harsh elution conditions resulted in a highly specific isolation of hydrophobin SC3 from the model mixture of ten proteins. The presented isolation protocol can have a positive impact on the analysis and utilization of these proteins including all class I hydrophobins. Hydrophobin SC3 was further subjected to reduction of its highly stable disulfide bonds and to chymotryptic digestion followed by mass spectrometric analysis. The isolation and digestion protocols presented in this work make the analysis of these highly hydrophobic and compact proteins possible.
- MeSH
- albuminy chemie MeSH
- ananasovník chemie MeSH
- bromelainy chemie MeSH
- Canavalia chemie MeSH
- chymotrypsin chemie MeSH
- cytochromy c chemie MeSH
- disulfidy chemie MeSH
- erytrocyty enzymologie MeSH
- extrakce na pevné fázi metody MeSH
- hmotnostní spektrometrie metody MeSH
- karboanhydrasy chemie MeSH
- kaseiny chemie MeSH
- koně MeSH
- konkanavalin A chemie MeSH
- kur domácí MeSH
- lidé MeSH
- mikrosféry * MeSH
- mléko enzymologie MeSH
- myokard metabolismus MeSH
- polytetrafluoroethylen chemie MeSH
- proteomika metody MeSH
- Schizophyllum chemie MeSH
- skot MeSH
- spektrometrie hmotnostní - ionizace laserem za účasti matrice MeSH
- tandemová hmotnostní spektrometrie MeSH
- thermolysin chemie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- skot MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
The antiurease activity of the aqueous extracts of 42 plants growing in the Czech Republic was investigated. A phenol-hypochlorite reaction was used for the determination of ammonia produced by urease. The inhibitory activity of the extracts at a concentration of 0.2 mg/mL varied from 17.8% to 80.0%. Extracts from six Potentilla species expressed inhibitory activity against jack bean urease. They were further investigated for their phenolic constituents and the major compounds were subjected to molecular docking. The results revealed that both jack bean urease and Helicobacter pylori urease were inhibited by quercetin-3-O-β-D-galactopyranoside-6″-gallate (1), myricetin-3-O-β-D-glucuronide (2), tiliroside (3) and B-type procyanidin (4). The antiurease activity of the investigated Potentilla species is probably due to the presence of complex phenolic constituents such as flavonoid glycosides and catechin dimers.
- MeSH
- algoritmy MeSH
- Canavalia enzymologie MeSH
- fenoly chemie izolace a purifikace farmakologie MeSH
- flavonoidy chemie izolace a purifikace farmakologie MeSH
- galaktosidy chemie izolace a purifikace farmakologie MeSH
- Helicobacter pylori účinky léků MeSH
- infekce vyvolané Helicobacter pylori farmakoterapie MeSH
- léčivé rostliny chemie MeSH
- Potentilla chemie MeSH
- quercetin analogy a deriváty MeSH
- ureasa antagonisté a inhibitory MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Česká republika MeSH
