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doctoral thesis
Racionalni dizajn, sinteza i biološko profiliranje novih JMJD2C inhibitora
2020. urn:nbn:hr:193:405367
Leftus, Vatroslav
University of Rijeka
Faculty of Biotechnology and Drug Development

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Leftus, V. (2020). Racionalni dizajn, sinteza i biološko profiliranje novih JMJD2C inhibitora (Doctoral thesis). Rijeka: University of Rijeka. Retrieved from https://urn.nsk.hr/urn:nbn:hr:193:405367

Leftus, Vatroslav. "Racionalni dizajn, sinteza i biološko profiliranje novih JMJD2C inhibitora." Doctoral thesis, University of Rijeka, 2020. https://urn.nsk.hr/urn:nbn:hr:193:405367

Leftus, Vatroslav. "Racionalni dizajn, sinteza i biološko profiliranje novih JMJD2C inhibitora." Doctoral thesis, University of Rijeka, 2020. https://urn.nsk.hr/urn:nbn:hr:193:405367

Leftus, V. (2020). 'Racionalni dizajn, sinteza i biološko profiliranje novih JMJD2C inhibitora', Doctoral thesis, University of Rijeka, accessed 20 November 2024, https://urn.nsk.hr/urn:nbn:hr:193:405367

Leftus V. Racionalni dizajn, sinteza i biološko profiliranje novih JMJD2C inhibitora [Doctoral thesis]. Rijeka: University of Rijeka; 2020 [cited 2024 November 20] Available at: https://urn.nsk.hr/urn:nbn:hr:193:405367

V. Leftus, "Racionalni dizajn, sinteza i biološko profiliranje novih JMJD2C inhibitora", Doctoral thesis, University of Rijeka, Rijeka, 2020. Available at: https://urn.nsk.hr/urn:nbn:hr:193:405367

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Metadata
TitleRacionalni dizajn, sinteza i biološko profiliranje novih JMJD2C inhibitora
Title (english)Rational design, synthesis and biological profiling of new JMJD2C inhibitors
AuthorVatroslav Leftus
MentorSanja Koštrun (mentor)
Committee memberKarlo Wittine (predsjednik povjerenstva)
Committee memberMarta Žuvić (član povjerenstva)
Committee memberJelena Ban (član povjerenstva)
Committee memberSanja Koštrun (član povjerenstva)
GranterUniversity of Rijeka
(Faculty of Biotechnology and Drug Development)
Rijeka
Defense date and country2020-11-09, Croatia
Scientific / art field,
discipline and subdiscipline		BIOTECHNICAL SCIENCES
Biotechnology
Universal decimal classification
(UDC)		577 - Biochemistry. Molecular biology. Biophysics
Abstract
JMJD2 je enzimska obitelj humanih histon demetilaza koje su povezane s bolestima kao što su karcinom dojke i prostate. Ti enzimi smatraju se onkogenima i njihova selektivna inhibicija mogla bi biti pristup za tretiranje spomenutih karcinoma. Literaturno poznati inhibitori imaju nisku staničnu permeabilnost i selektivnost, zbog čega su daljnja istraživanja usmjerena napoboljšanje aktivnosti, selektivnosti i ADME svojstava. U ovom istraživanju korišteni su dostupni literaturni podaci o poznatim inhibitorima kao kristalne strukture enzima JMJD2A/JMJD2C u kompleksu s malim molekulama. Analizom literaturno dostupnih kristalnih struktura proučene su interakcije između proteina i liganda te su metodama molekulskog modeliranja dizajnirani i zatim sintetizirani novi potencijalni inhibitori s toksoflavinskim strukturnim motivom. Kroz biološko profiliranje supstanci u in vitro pokusima određena je njihova inhibicijska aktivnost na JMJD2C enzimu, zatim stanična permeabilnost i metabolička stabilnost molekula, te utjecaj na viabilnost stanica.
Abstract (english)
JMJD2 is human histone demethylase family of enzimes that are linked to diseases such as prostate and breast cancer. These enzymes are considered oncogenes and their selective inhibition might be a therapeutic approach to treat the cancer. Currently known inhibitors have low permeability and low selectivity, so the further investigation is focused on optimizing activity, selectivity and ADME data. In my thesis I used available literature data on known inhibitors and x-ray structures of JMJD2C complexes with small molecules. A computational analysis of protein-ligand interactions was applied using structure based drug design tools to design potential JMJD2C inhibitors with a toxoflavin motif. Chemical synthesis of designed compounds was developed. New compounds were profiled in vitro on JMJD2C enzyme inhibition, membrane permeability and microsomal stability as well as their influence on cell viability.
Keywords
Keywords (english)
Languagecroatian
URN:NBNurn:nbn:hr:193:405367
Promotion2023
Study programmeTitle: Medicinal chemistry
Study programme type: university
Study level: postgraduate
Academic / professional title: doktor/doktorica znanosti, interdisciplinarna područja znanosti, polje biotehnologija u biomedicini (doktor/doktorica znanosti, interdisciplinarna područja znanosti, polje biotehnologija u biomedicini)
Type of resourceText
File originBorn digital
Access conditionsOpen access
Terms of useLicence In copyright icon
Created on2023-10-11 10:25:17