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master's thesis
Istraživanje interakcije spojeva iz masline s tirozin kinazom HGFR/C-MET pomoću molekulskog uklapanja
Zagreb: University of Zagreb, Faculty of Pharmacy and Biochemistry, 2023. urn:nbn:hr:163:244119
Jagar, Fran
University of Zagreb
Faculty of Pharmacy and Biochemistry
Department of medicinal chemistry

Institutional repository: Repository of Faculty of Pharmacy and Biochemistry University of Zagreb

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Jagar, F. (2023). Istraživanje interakcije spojeva iz masline s tirozin kinazom HGFR/C-MET pomoću molekulskog uklapanja (Master's thesis). Zagreb: University of Zagreb, Faculty of Pharmacy and Biochemistry. Retrieved from https://urn.nsk.hr/urn:nbn:hr:163:244119

Jagar, Fran. "Istraživanje interakcije spojeva iz masline s tirozin kinazom HGFR/C-MET pomoću molekulskog uklapanja." Master's thesis, University of Zagreb, Faculty of Pharmacy and Biochemistry, 2023. https://urn.nsk.hr/urn:nbn:hr:163:244119

Jagar, Fran. "Istraživanje interakcije spojeva iz masline s tirozin kinazom HGFR/C-MET pomoću molekulskog uklapanja." Master's thesis, University of Zagreb, Faculty of Pharmacy and Biochemistry, 2023. https://urn.nsk.hr/urn:nbn:hr:163:244119

Jagar, F. (2023). 'Istraživanje interakcije spojeva iz masline s tirozin kinazom HGFR/C-MET pomoću molekulskog uklapanja', Master's thesis, University of Zagreb, Faculty of Pharmacy and Biochemistry, accessed 26 November 2024, https://urn.nsk.hr/urn:nbn:hr:163:244119

Jagar F. Istraživanje interakcije spojeva iz masline s tirozin kinazom HGFR/C-MET pomoću molekulskog uklapanja [Master's thesis]. Zagreb: University of Zagreb, Faculty of Pharmacy and Biochemistry; 2023 [cited 2024 November 26] Available at: https://urn.nsk.hr/urn:nbn:hr:163:244119

F. Jagar, "Istraživanje interakcije spojeva iz masline s tirozin kinazom HGFR/C-MET pomoću molekulskog uklapanja", Master's thesis, University of Zagreb, Faculty of Pharmacy and Biochemistry, Zagreb, 2023. Available at: https://urn.nsk.hr/urn:nbn:hr:163:244119

Metadata
TitleIstraživanje interakcije spojeva iz masline s tirozin kinazom HGFR/C-MET pomoću molekulskog uklapanja
Title (english)Study of interactions between olive compounds and tyrosine kinase HGFR/C-MET using molecular docking
AuthorFran Jagar
MentorVišnja Stepanić (mentor)
MentorMonika Barbarić (mentor)
Committee memberVišnja Stepanić (predsjednik povjerenstva)
Committee memberMonika Barbarić (član povjerenstva)
Committee memberCvijeta Jakobušić Brala (član povjerenstva)
GranterUniversity of Zagreb
Faculty of Pharmacy and Biochemistry
(Department of medicinal chemistry)
Zagreb
Defense date and country2023-03-16, Croatia
Scientific / art field,
discipline and subdiscipline		BIOMEDICINE AND HEALTHCARE
Pharmacy
Pharmacy
Abstract
Protein kinaze su enzimi koji kataliziraju proces fosforilacije, poznati su onkogeni i posreduju većini prijenosa signala u eukariotskim stanicama modifikacijom aktivnosti proteinskih supstrata, kontroliranjem mnogih staničnih procesa poput metabolizma, transkripcije gena, progresije staničnog ciklusa, preuređivanja citoskeleta i kretanja stanica, apoptoze i diferencijacije stanica. Glavna uloga kinaza u patofiziologiji bolesti istaknuta je nakon otkrića da mutacije kinaza mogu dovesti do dijabetesa, karcinoma, kardiovaskularnih, neurodegenerativnih, razvojnih i imunosnih poremećaja. Protein kinaze važne su kliničke mete brojnih inhibitora kinaza u kliničkoj praksi te u kliničkim ispitivanjima. Predmet in silico istraživanja ovog diplomskog rada je bio receptor za faktor rasta hepatocita (Hepatocyte growth factor receptor, HGFR) koji je finalni produkt transkripcije (proto-onko) gena MET, a naziva se još i c-Met kinaza. Inhibitorna aktivnost odabranih spojeva iz masline (Olea europea L.) na c-Met kinazi ispitivana je procesom molekulskog uklapanja (program Maestro), jednim od najmodernijih pristupa u ispitivanju potencijalnih novih lijekova. Za potrebe istraživačkog dijela ovog rada formirana je biblioteka od dvije podgrupe spojeva: 17 spojeva koji su poznati inhibitori HGFR/c-Met kinaze i 31 spoj koji se nalaze u maslini (Olea europea L.). Dobiveni rezultati sugerirali su kako bi flavonoidi diosmetin, apigenin, luteolin i kvercetin mogli imati inhibitorni učinak, , što je u skladu s literaturnim podacima. Kao mogući novi ATP-kompetitivni inhibitori kinaze c-Met otkriveni su i lignani berhemol (u 2R, 3S, 4R konfiguraciji), (+)-verukozin i (+)-pinorezinol što bi trebalo potvrditi daljnjim in vitro testiranjem.
Abstract (english)
Protein kinases are enzymes which catalyze the process of phosphorylation, they are known ocogenes and mediate many cellular signaling pathways by modification of substrate activity and controlling many cell processes like metabolism, gene transcription, cell cycle activity, cytoskeletal rearrangement, apoptosis and differentiation. The key role of kinases in disease pathophysiology is underscored by the finding that mutation in kinases can lead to diabetes, cancer, cardiovascular, neurodegenerative, developmental, immune and behavioral disorders. Protein kinases are important clinical targets of numerous kinase inhibitors in clinical use or undergoing clinical trials. The main subject of this study is the kinase Hepatocyte growth factor receptor which is also called c-Met kinase and is the final product of the (proto-onco) gene MET transcription. Molecular docking, which is one of the newest approaches in drug discovery, was used for examination of the potential inhibitory activity of the selected compounds found in olive plant (Olea europea L.) on the c-Met kinase. The group of molecules selected for examination in this study (library) was made of 17 known c-Met kinase inhibitors and 31 compounds found in olive plant (Olea europea L.). The obtained results suggest that the flavonoids diosmetin, apigenin, luteolin and quercetin could have an inhibitory effect, which is in accordance with literature data. As possible novel ATP-competitive inhibitors of c-Met kinase, the lignans berhemol (u 2R, 3S, 4R stereoconfiguration), (+)-verrucosin and (+)-pinoresinol are also discovered, which should be confirmed by further in vitro testing.
Keywords
Keywords (english)
Languagecroatian
URN:NBNurn:nbn:hr:163:244119
Study programmeTitle: Pharmacy
Study programme type: university
Study level: integrated undergraduate and graduate
Academic / professional title: magistar/magistra farmacije (magistar/magistra farmacije)
Type of resourceText
File originBorn digital
Access conditionsOpen access
Terms of useLicence In copyright icon
Created on2023-03-16 11:35:36