Interakcije 4''-piridin-3-il- i 4''-(4-trifluormetoksifenil)-makrozona s biološkim metama

master's thesis

• Title (english): Interactions of 4''-pyridine-3-yl- and 4''-(4 -trifluoromethoxyphenyl)-macrozones with biological targets
• Author: Monika Kapustić
• Mentor: Tomislav Jednačak (mentor)
• Committee member: Tomislav Jednačak (predsjednik povjerenstva)
• Committee member: Mirta Rubčić (član povjerenstva)
• Committee member: Nikola Cindro (član povjerenstva)
• Committee member: Predrag Novak (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Chemistry); Zagreb
• Defense date and country: 2023-03-17, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Chemistry

Abstract

Makrolidni antibiotici pripadaju skupni makrolida koji se široko primjenjuju za liječenje
infekcija gornjih i donjih dišnih puteva. Mehanizam djelovanja makrolida temelji se na
vezanju za 23S rRNA u peptidil-transferaznom centru bakterijskog ribosoma ili u njegovoj
blizini, što sprječava izlaz novosintetiziranih peptida i inhibira sintezu proteina. Pojava
višestruke bakterijske rezistencije predstavlja ozbiljnu prijetnju za ljudsko zdravlje, što je
potaknulo sintezu novih derivata makrolida koji će pokazivati bolju bioaktivnost. Vezanjem
poznatih makrolida i bioaktivnih tiosemikarbazona dobiveni su novi konjugati, makrozoni,
koji uspješno djeluju protiv nekih rezistentnih bakterijskih sojeva.
U ovom radu okarakterizirane su interakcije nekoliko 4''-aril-makrozona s biološkim metama,
poput albumina iz goveđeg seruma te ribosoma iz bakterije Escherichia coli. Istraživanja su
provedena kombinacijom metoda spektrofluorimetrije, spektrofotometrije i cirkularnog
dikroizma. Kao kompetitor u fluorimetrijskim mjerenjima korišten je flourescirajući derivat
azitromicina, 9a-NBD-azitromicin. Podaci su zatim obrađeni metodama multivarijatne analize
kako bi se odredile konstante vezanja.

Abstract (english)

Due to their anti-infective activity, macrolide antibiotics (macrolides) are widely used for the
treatment of upper and lower respiratory tract infections. Their mechanism of action is based
on reversible binding to 23S rRNA at or near the peptidyl-transferase center of the bacterial
ribosome, which prevents the release of newly synthesized peptides and inhibits the protein
synthesis. The emergence of bacterial resistance represents a serious threat to human health,
which prompted the synthesis of new macrolide derivatives with a better bioactivity. Linking
known macrolides to bioactive thiosemicarbazones resulted with new conjugates,
macrozones, active against some resistant bacterial strains.
In this work, the interactions of several 4''-aryl-macrozones with biological targets, such as
bovine serum albumin and Escherichia coli ribosomes, were characterized. The studies were
carried out by combining spectrofluorimetric, spectrophotometric and circular dichroism
methods. Competition fluorimetric experiments were conducted using a fluorescent derivative
of azithromycin, 9a-NBD-azithromycin. The data were further processed with multivariate
analysis methods to determine the binding constants.

• Keywords: bakterije; makrolidi; makrozoni; rezistencija; ribosom; spektrofluorimetrija
• Keywords (english): bacteria; macrolides; macrozones; resistance; ribosome; spectrofluorimetry
• Language: croatian
• URN:NBN: urn:nbn:hr:217:127491
• Project: Number: IP-2018-01-8098; Title: Makrozoni, novi konjugati makrolidnih antibiotika: Dizajn, priprava i interakcije; Title: Macrozones, New Conjugates of Macrolide Antibiotics: Design, Synthesis and Interactions; Acronym: Makrozoni/Macrozones; Leader: Predrag Novak; Jurisdiction: Croatia; Funder: HRZZ; Funding stream: IP
• Study programme: Title: Graduate university studies in chemistry; specializations in: Research programme; Course: Research programme; Study programme type: university; Study level: graduate; Academic / professional title: magistar/magistra kemije (magistar/magistra kemije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Embargoed access; Embargo expiration date: 2025-03-17
• Created on: 2023-04-03 09:16:47