The interactions of epoxiconazole and prothioconazole with human serum albumin and bovine serum albumin were investigated using spectroscopic methods complemented with molecular modeling. Spectroscopic techniques showed the formation of pesticide/serum albumin complexes with the static type as the dominant mechanism. The association constants ranged from 3.80 × 104-6.45 × 105 L/mol depending on the pesticide molecule (epoxiconazole, prothioconazole) and albumin type (human or bovine serum albumin). The calculated thermodynamic parameters revealed that the binding of pesticides into serum albumin macromolecules mainly depended on hydrogen bonds and van der Waals interactions. Synchronous fluorescence spectroscopy and the competitive experiments method showed that pesticides bind to subdomain IIA, near tryptophan; in the case of bovine serum albumin also on the macromolecule surface. Concerning prothioconazole, we observed the existence of an additional binding site at the junction of domains I and III of serum albumin macromolecules. These observations were corroborated well by molecular modeling predictions. The conformation changes in secondary structure were characterized by circular dichroism, three-dimensional fluorescence, and UV/VIS absorption methods.
- MeSH
- cirkulární dichroismus metody MeSH
- epoxidové sloučeniny chemie MeSH
- fluorescenční spektrometrie metody MeSH
- hydrofobní a hydrofilní interakce MeSH
- lidé MeSH
- lidský sérový albumin chemie MeSH
- pesticidy chemie MeSH
- sekundární struktura proteinů MeSH
- sérový albumin hovězí chemie MeSH
- simulace molekulového dockingu metody MeSH
- skot MeSH
- statická elektřina MeSH
- teplota MeSH
- triazoly chemie MeSH
- vazba proteinů MeSH
- vazebná místa MeSH
- vodíková vazba MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- skot MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Photosensitive compounds found in herbs have been reported in recent years as having a variety of interesting medicinal and biological activities. In this review, we focus on photosensitizers such as hypericin and its model compounds emodin, quinizarin, and danthron, which have antiviral, antifungal, antineoplastic, and antitumor effects. They can be utilized as potential agents in photodynamic therapy, especially in photodynamic therapy (PDT) for cancer. We aimed to give a comprehensive summary of the physical and chemical properties of these interesting molecules, emphasizing their mechanism of action in relation to their different interactions with biomacromolecules, specifically with DNA.
- MeSH
- anthrachinony chemie MeSH
- antitumorózní látky chemie farmakologie MeSH
- fotochemoterapie MeSH
- fotosenzibilizující látky chemie farmakologie MeSH
- lidé MeSH
- nádory farmakoterapie MeSH
- perylen analogy a deriváty chemie farmakologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
The application of pesticides and chemical fertilizers constitutes a potential risk to human and animals due to the presence of their residues in the food. Thiacloprid belongs to a group of neonicotinoid insecticides. It shows a cytotoxic/cytostatic effect in human peripheral blood lymphocytes probably due to DNA damage. The use of thiacloprid is increasingly widespread worldwide, therefore is very important the assessment of its possible genotoxic and cytotoxic effects on a living organism. That is the reason why we studied the thiacloprid influence on the structure and stability of DNA in presented work. We have been studied the thiacloprid interaction with calf thymus DNA. Association constant was determined by fluorescence spectroscopy using equilibrium receptor-ligand binding analysis. The thermal denaturation of DNA was used to identify the mode of interaction. Viscosity changes were recorded to confirm/disconfirm the intercalation mode of interaction. Given the results, we can conclude that neonicotinoid pesticide thiacloprid destabilizes DNA. It changes the structure and stability of DNA through binding into the minor groove by hydrophobic or hydrogen interactions.
Studies of interactions between pesticides and target mammalian proteins are important steps toward understanding the pesticide's toxicity. Using calorimetric and spectroscopic methods, the interaction between triazole fungicide tebuconazole and human serum albumin has been investigated. The spectroscopic techniques showed that fluorescence quenching of human serum albumin by tebuconazole was the result of the formation of tebuconazole/human serum albumin complex with the static type as the dominant mechanism. The association constant was found to be 8.51 × 103 L/mol. The thermodynamic parameters were obtained as ΔH = -56.964 kJ/mol, ΔS = -115.98 J/mol·K. The main active interactions forming the tebuconazole/human serum albumin complex were identified as the interplay between hydrogen bonds and/or van der Waals forces, based on thermodynamic experiments. These binding modes were corroborated well by the predictions of molecular modeling. Hydrogen bonding of tebuconazole with Arg222, Ala215 and Ala291 of human serum albumin played a relevant role in binding. The conformation changes in secondary structure were characterized by circular dichroism and 3D fluorescence spectra.
- MeSH
- diferenciální skenovací kalorimetrie MeSH
- fluorescenční spektrometrie MeSH
- fungicidy průmyslové farmakologie MeSH
- ibuprofen farmakologie MeSH
- ketoprofen farmakologie MeSH
- lidé MeSH
- lidský sérový albumin chemie metabolismus MeSH
- simulace molekulového dockingu MeSH
- termodynamika MeSH
- triazoly chemie farmakologie MeSH
- vazba proteinů MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND/AIM: We report the incorporation of prospective anticancer agent hypericin into DNA and bovine serum albumin (BSA), respectively, with emphasis on comparison of the differences in interaction mode between hypericin and its model compound emodin. MATERIALS AND METHODS: Spectrophotometric methods were used for determination of the binding constants of the drug complex with biomacromolecules. Differential scanning calorimetry was applied for evaluation of drug-macromolecule complex thermal stability. RESULTS: The strength of interaction expressed by binding constants was found to be 4.0×104 l/mol for hypericin-DNA and 8.1×104 l/mol for emodin-DNA complex. Both molecules stabilize bovine serum albumin macromolecule and bind into the hydrophobic cavity in IIA subunit but their localization within the molecule is different. CONCLUSION: Anticancer agent hypericin and its derivative emodin interact with DNA with medium strength and are probably incorporated into the groove of DNA by hydrogen bonds. Bovine serum albumin can serve as a transport protein for hypericin since the binding force between both molecules is adequate.
- MeSH
- antitumorózní látky chemie farmakologie MeSH
- DNA chemie metabolismus MeSH
- emodin chemie farmakologie MeSH
- molekulární struktura MeSH
- perylen analogy a deriváty chemie farmakologie MeSH
- sérový albumin hovězí chemie metabolismus MeSH
- spektrální analýza MeSH
- termodynamika MeSH
- vazba proteinů MeSH
- vztahy mezi strukturou a aktivitou MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
By means of fluorescence microscopy the intracellular distribution of fluorescent drugs with different hydrophobicity (quinizarin, emodin and hypericin) was studied. Selective photoactivation of these drugs in precisely defined position (nuclear envelope) allowed moderately hydrophobic emodin enter the nucleus. Highly hydrophobic hypericin was predominantly kept in the membranes with no fluorescence observed in the nucleus. The redistribution of quinizarin, emodin and hypericin between lipids, proteins and DNA was studied in solutions and cells. Based on these results was proposed theoretical model of hydrophobic drugs' nuclear internalization after photo-activation. Molecular docking models showed that hypericin has the strongest affinity to P-glycoprotein involved in the cell detoxification. Presence of 10 μM quinizarin, emodin or hypericin increased P-glycoprotein function in U87 MG cells. Moreover, emodin pretreatment allowed quinizarin nuclear internalization without photo-activation, which was not the case for hypericin. The synergy of such pretreatment and photo-activation should lessen the drug doses with simultaneous increase of drug efficacy triggering cell apoptosis/necrosis.
- MeSH
- anthrachinony chemie farmakologie účinky záření MeSH
- buněčné jádro metabolismus účinky záření MeSH
- DNA chemie MeSH
- emodin chemie farmakologie účinky záření MeSH
- gliom metabolismus MeSH
- hydrofobní a hydrofilní interakce MeSH
- LDL-cholesterol chemie MeSH
- lidé MeSH
- nádorové buněčné linie MeSH
- P-glykoprotein metabolismus MeSH
- perylen analogy a deriváty chemie farmakologie účinky záření MeSH
- sérový albumin chemie MeSH
- simulace molekulového dockingu MeSH
- světlo MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
