- MeSH
- alergie epidemiologie etiologie prevence a kontrola MeSH
- biotechnologie metody MeSH
- fytoterapie MeSH
- infekce dýchací soustavy farmakoterapie prevence a kontrola MeSH
- kyseliny kávové chemie škodlivé účinky MeSH
- lidé MeSH
- propolis * chemie imunologie terapeutické užití MeSH
- rostlinné pryskyřice terapeutické užití MeSH
- Check Tag
- lidé MeSH
A small molecule EGFR inhibitor, 4-(2-(3-(4-(4-(trifluoromethyl)phenyl)thiazol-2-yl)ureido)vinyl)-1,2-phenylene diacetate (CIU1) was designed in silico by using caffeic scaffold as core structure. The designed compound showed anti-proliferative action against different solid tumor cell lines, particularly metastatic breast cancer cells. CIU1 inhibited the growth of EGFR-overexpressing MDA-MB-468 triple-negative breast cancer cells and wild-type non-small-cell lung cancer H460 cells with IC50 values of 8.96 μM and 12.98 μM, respectively, these anti-proliferative effects of CIU1 were comparable to gefitinib (a specific EGFR inhibitor) or lapatinib (a dual EGFR and HER2 tyrosine kinase inhibitor). Interestingly CIU1 effectively inhibited the invasive hormone-dependent MCF-7 cancer cells with an IC50 2.34 μM. The immunoblot analyses revealed that CIU1 induced programmed cell death and suppressed EGFR expression in EGFR-overexpressing breast cancer (MDA-MB468) and lung cancer (PC-9) cells. The findings substantiated our design strategy and demonstrated the potential of CIU1 as new lead for further optimization in the development of anticancer drugs against advanced solid tumors.
- MeSH
- erbB receptory antagonisté a inhibitory chemie MeSH
- kyseliny kávové chemie MeSH
- metastázy nádorů MeSH
- molekulární modely MeSH
- molekulární sondy - techniky MeSH
- nemalobuněčný karcinom plic farmakoterapie MeSH
- proliferace buněk MeSH
- triple-negativní karcinom prsu farmakoterapie MeSH
- Publikační typ
- hodnotící studie MeSH
- práce podpořená grantem MeSH
Preparation of coated pellets intended for rutin colon delivery, their evaluation in vitro and in vivo in experimental colitis in rats was the purpose of this study. Pellets were obtained using extrusion/spheronization and coated with three types of coatings (caffeic acid/hypromellose/alginic acid; sodium alginate/hypromellose/zinc acetate; sodium alginate/chitosan). Dissolution using buffers of pH values, β-glucosidase and times corresponding to gastrointestinal tract (GIT) was provided. Pellets coated with alginate/chitosan showed low rutin dissolution (12-14%) in upper GIT conditions and fast release (87-89%) under colon conditions; that is a good presumption of intended rutin release. After colitis induction and development, the rats were treated with pellets and rutin solution administered orally, solution also rectally. Colon/body weight ratio, myeloperoxidase activity and histological evaluation were performed. Rutin was able to promote colonic healing at the dose of 10mg/kg: colon/body weight ratio decreased and myeloperoxidase activity was significantly suppressed. Pellets coated with alginate/chitosan applied orally and rutin solution administered rectally showed the best efficacy. The combination of rutin as natural product, mucoadhesive chitosan degraded in the colon and sodium alginate as the main coating substance in the form of pellets create a promising preparation for therapy of this severe illness.
- MeSH
- algináty chemie MeSH
- antiflogistika aplikace a dávkování chemie farmakologie MeSH
- aplikace orální MeSH
- časové faktory MeSH
- chitosan chemie MeSH
- farmaceutická chemie MeSH
- farmaceutická technologie metody MeSH
- gastrointestinální látky aplikace a dávkování chemie farmakologie MeSH
- implantované léky MeSH
- kolitida chemicky indukované farmakoterapie patologie MeSH
- kolon účinky léků patologie MeSH
- koncentrace vodíkových iontů MeSH
- krysa rodu rattus MeSH
- kyselina glukuronová chemie MeSH
- kyselina trinitrobenzensulfonová MeSH
- kyseliny hexuronové chemie MeSH
- kyseliny kávové chemie MeSH
- methylcelulosa analogy a deriváty chemie MeSH
- modely nemocí na zvířatech MeSH
- octan zinečnatý chemie MeSH
- potkani Wistar MeSH
- příprava léků MeSH
- pufry MeSH
- rozpustnost MeSH
- rutin aplikace a dávkování chemie farmakologie MeSH
- stabilita léku MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
