Quercetin is one of the most prominent and widely studied flavonoids. Its oxidation has been previously investigated only indirectly by comparative analyses of structurally analogous compounds, e.g. dihydroquercetin (taxifolin). To provide direct evidence about the mechanism of quercetin oxidation, we employed selective alkylation procedures for the step-by-step blocking of individual redox active sites, i.e. the catechol, resorcinol and enol C-3 hydroxyls, as represented by newly prepared quercetin derivatives 1-3. Based on the structure-activity relationship (SAR), electrochemical, and computational (density functional theory) studies, we can clearly confirm that quercetin is oxidized in the following steps: the catechol moiety is oxidized first, forming the benzofuranone derivative via intramolecular rearrangement mechanism; therefore the quercetin C-3 hydroxy group cannot be involved in further oxidation reactions or other biochemical processes. The benzofuranone is oxidized subsequently, followed by oxidation of the resorcinol motif to complete the electrochemical cascade of reactions. Derivatization of individual quercetin hydroxyls has a significant effect on its redox behavior, and, importantly, on its antiradical and stability properties, as shown in DPPH/ABTS radical scavenging assays and UV-Vis spectrophotometry, respectively. The SAR data reported here are instrumental for future studies on the oxidation of biologically or technologically important flavonoids and other polyphenols or polyhydroxy substituted aromatics. This is the first complete and direct study mapping redox properties of individual moieties in quercetin structure.
Currently, chemotherapy is the most common treatment for oncological diseases. Systemic administration of chemotherapeutics provides an easy and effective distribution of the active agents throughout the patient's body, however organs may be severely impaired by serious life-threatening side effects. In many oncological diseases, particularly solid tumors, the local application of chemotherapeutics would be advantageous. Recently, nanofibrous materials as local drug delivery systems have attracted much attention. They have considerable potential in the treatment of various cancers as they can provide a high concentration of the drug at the target site for a prolonged time, thereby lowering total exposure and adverse effects. The present review describes the specifics of drug delivery to the tumor microenvironment, basic characteristics of nanofibrous materials and their preparation, and comprehensively summarizes recent scientific reports concerning in vivo experiments with drug-loaded electrospun nanofibrous systems designed for local anticancer therapy.
Polymeric bile acid sequestrants (BAS) have recently attracted much attention as lipid-lowering agents. These non-absorbable materials specifically bind bile acids (BAs) in the intestine, preventing bile acid (BA) reabsorption into the blood through enterohepatic circulation. Therefore, it is important to understand the structure-property relationships between the polymer sequestrant and its ability to bind specific BAs molecules. In this review, we describe pleiotropic effects of bile acids, and we focus on BAS with various molecular architectures that result in different mechanisms of BA sequestration. Here, we present 1) amphiphilic polymers based on poly(meth)acrylates, poly(meth)acrylamides, polyalkylamines and polyallylamines containing quaternary ammonium groups, 2) cyclodextrins, and 3) BAS prepared via molecular imprinting methods. The synthetic approaches leading to individual BAS preparation, as well as results of their in vitro BA binding activities and in vivo lipid-lowering activities, are discussed.
- MeSH
- anticholesteremika chemická syntéza chemie farmakologie MeSH
- hypercholesterolemie farmakoterapie MeSH
- lidé MeSH
- molekulární struktura MeSH
- polymery chemická syntéza chemie farmakologie MeSH
- racionální návrh léčiv * MeSH
- vazebná místa účinky léků MeSH
- žlučové kyseliny a soli chemická syntéza chemie farmakologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
