In vitro biološka evaluacija ferocenskih konjugata s aminokiselinama Val, Leu i Phe

master's thesis

• Title (english): In vitro biological evaluation of ferrocene conjugates with amino acids Val, Leu and Phe
• Author: Marina Ivančić
• Mentor: Lidija Barišić (mentor)
• Committee member: Kristina Radošević (predsjednik povjerenstva)
• Committee member: Marko Marjanović (član povjerenstva)
• Committee member: Monika Kovačević (član povjerenstva)
• Granter: University of Zagreb; Faculty of Food Technology and Biotechnology; (Department of Chemistry and Biochemistry); (Laboratory for Organic Chemistry); Zagreb
• Defense date and country: 2022-07-18, Croatia
• Scientific / art field, discipline and subdiscipline: BIOTECHNICAL SCIENCES; Biotechnology

Abstract

Strukturna modifikacija nativnih peptida predstavlja učinkovit pristup u dizajnu farmakološki aktivnih biomolekula. Konjugiranjem ferocenskih kalupa s aminokiselinama i malim peptidima pripravljaju se visokouređeni i biološki aktivni peptidomimetici. U cilju ispitivanja odnosa strukture i biološke aktivnosti peptidomimetika, u ovome radu provedena je in vitro biološka evaluacija dvanaest homo- i heterokiralnih konjugata ferocen-1,1'-diamina s Val (1−4), Leu (5−8) i Phe (9−12) na humanim tumorskim staničnim linijama (HeLa, MCF-7 i HepG2). Najveću antiproliferativnu aktivnost i toksičnost prema svim staničnim linijama pokazali su heterokiralni konjugati 2, 4, 6, 8 i 10. Sposobnost indukcije stanične smrti i narušavanje integriteta stanične membrane dodatno su ispitani analizom vezanja Annexina V i PI primjenom protočne citometrije tijekom 24- i 48-satnog tretmana stanica pri čemu se najučinkovitijim induktorom apoptoze pokazao heterokiralni Phe-peptid 10. Analizom staničnog ciklusa utvrđeni su zastoji unutar G1 ili G2/M faze tijekom 48-satnog tretmana stanica heterokiralnim peptidima 4, 8 i 10, što dodatno ukazuje na njihov antitumorski potencijal.

Abstract (english)

Structural modification of native peptides represents an effective approach for the design of pharmacologically active biomolecules. Highly ordered and biologically active peptidomimetics were prepared by conjugation of the ferrocene scaffold with amino acids and small peptides. In this work, twelve homo- and heterochiral conjugates of ferrocene-1,1'-diamine with Val (1-4), Leu (5-8), and Phe (9-12) were biologically studied in vitro on human tumor cell lines (HeLa, MCF-7 and HepG2). Heterochiral conjugates 2, 4, 6, 8 and 10 showed the greatest antiproliferative activity and toxicity to all cell lines. The ability to induce cell death and affect cell membrane integrity was examined by analysis of Annexin V and PI staining using flow cytometry during 24- and 48-hour treatment of cells, with heterochiral Phe-peptide 10 being the most effective in inducing apoptosis. Cell cycle analysis revealed delays within G1 or G2/M phase during 48-hour treatment with heterochiral peptides 4, 8 and 10, providing further evidence of their anticancer potential.

• Keywords: erocen; peptidomimetici; in vitro biološka evaluacija; antitumorski učinak; protočna citometrija
• Keywords (english): ferrocene; peptidomimetics; in vitro biological evaluation; antitumor activity; flow cytometry
• Language: croatian
• URN:NBN: urn:nbn:hr:159:492271
• Study programme: Title: Bioprocess Engineering; Study programme type: university; Study level: graduate; Academic / professional title: magistar/magistra inženjer/inženjerka bioprocesnog inženjerstva (magistar/magistra inženjer/inženjerka bioprocesnog inženjerstva)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2023-06-07 07:59:23