Chrysin Dotaz Zobrazit nápovědu
Synthesis of 7-(4-bromobutoxy)-5-hydroxy-2-phenyl-4H-chromen-4-one intermediate treating chrysin with 1,4-dibromobutane facilitated combination of chrysin with a wide range of piperazine moieties which were equipped via reacting the corresponding amines with bis(2-chloroethyl)amine hydrochloride in diethylene glycol monomethyl ether solvent. Free radical scavenging potential of prepared products was analyzed in vitro adopting DPPH and ABTS bioassay in addition to the evaluation of in vitro anticancer efficacies against cervical cancer cell lines (HeLa and CaSki) and an ovarian cancer cell line SK-OV-3 using SRB assay. Bearable toxicity of 7a-w was examined employing Madin-Darby canine kidney (MDCK) cell line. In addition, cytotoxic nature of the presented compounds was inspected utilizing Human bone marrow derived mesenchymal stem cells (hBM-MSCs). Overall, 7a-w indicated remarkable antioxidant power in scavenging DPPH(·) and ABTS(·+), particularly analogs 7f, 7j, 7k, 7l, 7n, 7q, 7v, 7w have shown promising free radical scavenging activity. Analogs 7j and 7o are identified to be highly active candidates against HeLa and CaSki cell lines, whereas 7h and 7l along with 7j proved to be very sensitive towards ovarian cancer cell line SKOV-3. None of the newly prepared scaffolds showed cytotoxic nature toward hBM-MSCs cells. From the structure-activity point of view, nature and position of the electron withdrawing and electron donating functional groups on the piperazine core may contribute to the anticipated antioxidant and anticancer action. Different spectroscopic techniques (FT-IR, (1)H NMR, (13)C NMR, Mass) and elemental analysis (CHN) were utilized to confirm the desired structure of final compounds.
- MeSH
- antioxidancia chemie farmakologie MeSH
- antitumorózní látky chemie farmakologie MeSH
- buněčné linie MeSH
- chemie farmaceutická MeSH
- flavonoidy chemie farmakologie MeSH
- lidé MeSH
- molekulární struktura MeSH
- piperaziny chemie farmakologie MeSH
- psi MeSH
- vztahy mezi strukturou a aktivitou MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- psi MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
7-(4-Bromobutoxy)-5-hydroxy-2-phenyl-4H-chromen-4-one, obtained from chrysin with 1,4-dibromobutane, was combined with a wide range of 6-substituted 2-aminobenzthiazoles, which had been prepared from the corresponding anilines with potassium thiocyanate. Free radical scavenging efficacies of newer analogues were measured using DPPH and ABTS assays, in addition to the assessment of their anticancer activity against cervical cancer cell lines (HeLa and CaSki) and ovarian cancer cell line (SK-OV-3) implementing the SRB assay. Cytotoxicity of titled compounds was checked using Madin-Darby canine kidney (MDCK) non-cancer cell line. Overall, 6a-r indicated remarkable antioxidant power as DPPH and ABTS(+) scavengers; particularly the presence of halogen(s) (6g, 6h, 6j-6l) was favourable with IC50 values comparable to the control ascorbic acid. Unsubstituted benzothiazole ring favored the activity of resultant compounds (6a and 6r) against HeLa cell line, whereas presence of chlorine (6g) or a di-fluoro group (6k) was a key to exert strong action against CaSki. Moreover, a mono-fluoro (6j) and a ketonic functionality (6o) were beneficial to display anticipated anticancer effects against ovarian cancer cell line SK-OV-3. The structural assignments of the new products were done on the basis of IR, (1)H NMR, (13)C NMR spectroscopy and elemental analysis.
- MeSH
- antioxidancia chemická syntéza chemie farmakologie MeSH
- antitumorózní látky chemická syntéza chemie farmakologie MeSH
- benzothiazoly chemická syntéza chemie farmakologie MeSH
- buňky MDCK MeSH
- flavonoidy chemická syntéza chemie farmakologie MeSH
- HeLa buňky MeSH
- inhibiční koncentrace 50 MeSH
- lidé MeSH
- molekulární struktura MeSH
- nádorové buněčné linie MeSH
- preklinické hodnocení léčiv MeSH
- psi MeSH
- viabilita buněk účinky léků MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- psi MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
The constitutive androstane receptor (CAR) is a crucial transcriptional regulator of key xenobiotic-metabolizing enzymes such as cytochrome P450 CYP3A4, CYP2C9 and CYP2B6. The flavonoids chrysin, baicalein and galangin have been reported to activate CAR and interfere with EGFR signaling. Nevertheless, it is not known if these flavonoids are direct CAR ligands or indirect phenobarbital-like CAR activators via the inhibition of epidermal growth factor receptor (EGFR) signaling. We analyze the interactions of chrysin, galangin and baicalein and its glycoside baicalin with human CAR. We have employed and validated methods that can study direct interaction with the CAR ligand binding pocket. Secondly, we determined if the compounds affect human EGFR signaling and interact with EGFR. Employing a TR-FRET coactivator assay with recombinant CAR or CAR assembly assay, a consistent activation of CAR with flavonoids and phenobarbital was not observed. It was determined, however, that galangin, chrysin, and baicalein may slightly repress EGFR-Tyr1068 autophosphorylation after EGF treatment, phosphorylation of downstream transcription factor ELK1 and stimulate EGFP-CAR nuclear translocation in primary human hepatocytes. These data suggest that flavonoids chrysin, galangin and baicalein are indirect human CAR activators. This study also demonstrates new approach how to test the direct CAR interaction with its ligands.
- MeSH
- buněčné linie MeSH
- cytochrom P450 CYP2B6 metabolismus MeSH
- erbB receptory účinky léků MeSH
- fenobarbital farmakologie MeSH
- flavanony farmakologie MeSH
- flavonoidy farmakologie MeSH
- hepatocyty účinky léků metabolismus MeSH
- lidé MeSH
- protein Elk-1 s doménou ets účinky léků genetika MeSH
- receptory cytoplazmatické a nukleární agonisté MeSH
- transport proteinů účinky léků MeSH
- vazebná místa účinky léků MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Klíčová slova
- Chrysin, Morin,
- MeSH
- finanční podpora výzkumu jako téma MeSH
- flavonoidy farmakologie MeSH
- hypertenze farmakoterapie MeSH
- krevní tlak účinky záření MeSH
- ledviny chemie účinky léků MeSH
- polyeny chemie MeSH
- potkani inbrední SHR MeSH
- quercetin farmakologie MeSH
- reaktivní formy kyslíku chemie MeSH
- srdce účinky léků MeSH
- synthasa oxidu dusnatého chemie účinky léků MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- abstrakt z konference MeSH
Strukturní rozmanitost obsahových látek propolisu, daná více rostlinnými zdroji, je příčinou proměnlivého složení a dosud nevyřešené standardizace. Hlavní podíl na biologických účincích je připisován flavonoidům a aromatickým kyselinám a jejich derivátům. Prezentované výsledky ilustrují proměnlivost ve složení deseti vzorků propolisu, získaných z různých oblastí ČR a dalších tří vzorků zahraničních. Pozornost byla věnována stanovení polyfenolů, obsahu flavonů a flavonolů a určení antioxidační aktivity. Výsledky potvrzují variabilitu sledovaných parametrů, i zastoupení chrysinu, galanginu, kyseliny p-kumarové, ferulové, skořicové a benzoové v závislosti na oblasti sběru. Bude obtížné vypracovat metodu standardizace, vhodnou pro možné aplikace propolisových přípravků. V budoucnu by se propolis mohl stát surovinou pro izolaci jednotlivých skupin biologicky aktivních látek.
The structural diversity of propolis constituents, due to a larger number of plant sources, is the cause of diverse composition and the hitherto unsolved standardization. The principal share in the biological effects is ascribed to flavonoids and aromatic acids and their derivatives. The results presented in this paper illustrate the diversity of the compositions of ten propolis samples obtained from different regions of the Czech Republic and three samples from abroad. Attention was paid to the determination of polyphenols, content of flavones and flavonols and the assay of antioxidative activity. The results confirmed the variability of the parameters under study as well as the presence of chrysin, galangin, p-coumaric, ferulic, cinnamic and benzoic acids in dependence on the area of collection. It will be difficult to elaborate a method of standardization suitable for possible administration of propolis preparations. In the future, propolis could become a raw material for the isolation of individual groups of biologically active substances.
1. Some flavonoids contained in the common diet have been shown to interact with important membrane uptake transporters, including organic anion transporting polypeptides (OATPs). OATP2B1 and OATP1A2 expressed in the apical membrane of human enterocytes may significantly contribute to the intestinal absorption of drugs, e.g. statins. This study is aimed at an evaluation of the inhibitory potency of selected food honey flavonoids (namely galangin, myricetin, pinocembrin, pinobanksin, chrysin and fisetin) toward hOATP2B1 and hOATP1A2 as well as at examining their effect on the cellular uptake of the known OATP substrate rosuvastatin. 2. Cell lines overexpressing the hOATP2B1 or hOATP1A2 transporter were employed as in vitro model to determine the inhibitory potency of the flavonoids toward the OATPs. 3. Chrysin, galangin and pinocembrin were found to inhibit both hOATP2B1 and hOATP1A2 in lower or comparable concentrations as the known flavonoid OATP inhibitor quercetin. Galangin, chrysin and pinocembrin effectively inhibited rosuvastatin uptake by hOATP2B1 with IC50 ∼1-10 μM. The inhibition of the hOATP1A2-mediated transport of rosuvastatin by these flavonoids was weaker. 4. The found data indicate that several of the tested natural compounds could potentially affect drug cellular uptake by hOATP2B1 and/or hOATP1A2 at relative low concentrations, a finding which suggests their potential for food-drug interactions.
- MeSH
- biologické modely MeSH
- buňky MDCK MeSH
- dieta MeSH
- flavonoidy farmakologie MeSH
- HEK293 buňky MeSH
- inhibiční koncentrace 50 MeSH
- lidé MeSH
- med * MeSH
- přenašeče organických aniontů antagonisté a inhibitory metabolismus MeSH
- psi MeSH
- rosuvastatin kalcium metabolismus MeSH
- transfekce MeSH
- transport proteinů účinky léků MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- psi MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Topical and transdermal drug delivery are advantageous administration routes, especially when treating diseases and conditions with a skin etiology. Nevertheless, conventional dosage forms often lead to low therapeutic efficacy, safety issues, and patient noncompliance. To tackle these issues, novel topical and transdermal platforms involving nanotechnology have been developed. This review focuses on the latest advances regarding the development of nanoemulgels for skin application, encapsulating a wide variety of molecules, including already marketed drugs (miconazole, ketoconazole, fusidic acid, imiquimod, meloxicam), repurposed marketed drugs (atorvastatin, omeprazole, leflunomide), natural-derived compounds (eucalyptol, naringenin, thymoquinone, curcumin, chrysin, brucine, capsaicin), and other synthetic molecules (ebselen, tocotrienols, retinyl palmitate), for wound healing, skin and skin appendage infections, skin inflammatory diseases, skin cancer, neuropathy, or anti-aging purposes. Developed formulations revealed adequate droplet size, PDI, viscosity, spreadability, pH, stability, drug release, and drug permeation and/or retention capacity, having more advantageous characteristics than current marketed formulations. In vitro and/or in vivo studies established the safety and efficacy of the developed formulations, confirming their therapeutic potential, and making them promising platforms for the replacement of current therapies, or as possible adjuvant treatments, which might someday effectively reach the market to help fight highly incident skin or systemic diseases and conditions.
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
