Priprava, karakterizacija i biološka aktivnost makrozona, novih derivata azitromicina

doctoral thesis

• Title (english): Preparation, characterization and biologial activity of macrozones, new azithromycin derivatives
• Author: Ivana Mikulandra
• Mentor: Predrag Novak (mentor)
• Committee member: Vesna Petrović-Peroković (predsjednik povjerenstva)
• Committee member: Dražen Vikić-Topić (član povjerenstva)
• Committee member: Ivo Piantanida (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Chemistry); Zagreb
• Defense date and country: 2022-06-14, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Chemistry
• Universal decimal classification (UDC): 54 - Chemistry. Crystallography. Mineralogy

Abstract

Značajan porast bakterijske rezistencije utječe na sve veću potrebu za istraživanjem i razvojem novih antibiotika. U sklopu ovog rada pripravljene su tri nove klase makrozona, konjugata makrolidnog antibiotika azitromicina i tiosemikarbazona. Tiosemikarbazoni su korišteni za kemijsku modifikaciju azitromicina na tri različita položaja. Cilj rada je priprava novih derivata makrolida sa širim spektrom biološke aktivnosti. Pripravljenim spojevima određena je biološka aktivnost in vitro na susceptibilne i rezistentne Gram-pozitivne i Gram-negativne bakterije te su istražene interakcije s biološkim receptorima. Za proučavanje interakcija primijenjena je spektroskopija NMR, cirkularni dikroizam, fluorescencijska spektroskopija i molekulsko modeliranje. Makrozoni su pokazali zadovoljavajuću biološku aktivnost, posebice na neke rezistentne bakterijske sojeve na koje azitromicin nije aktivan. Rezultati dobiveni spektroskopskim metodama i molekulskim modeliranjem ukazuju na odnos strukture i aktivnosti novih derivata azitromicina, što može poslužiti za dizajn i otkriće biaktivnijih derivata makrolida.

Abstract (english)

Owing to a significant increase in bacterial resistance, a high need for discovery and development of new antibiotics has emerged. As part of this work, three novel classes of macrozones, conjugates of macrolide antibiotic azithromycin and thiosemicarbazones, were prepared. Thiosemicarbazones were used to chemically modify azithromycin at three different positions. The aim of this thesis was to prepare compounds with a wider range of biological activity including resistant bacterial strains. In vitro biological activity of the prepared compounds was determined against susceptible and resistant Gram-positive and Gram-negative bacteria, and interactions with biological receptors were investigated. Macrozones showed satisfactory biological activity, especially against some resistant bacterial strains to which azithromycin is inactive. NMR spectroscopy, circular dichroism, fluorescence spectroscopy, and molecular modeling were further used to study interactions of selected compounds with biological targets. The results obtained by spectroscopic methods and molecular modeling indicate a relationship between structure and activity of new azithromycin derivatives, which can be used for design and discovery of more active macrolide derivatives.

• Keywords: azitromicin; biološka aktivnost; interakcije s biološkim metama; makrolidi; tiosemikarbazoni
• Keywords (english): azithromycin; biological activity; interactions with biological targets; macrolides; thiosemicarbazones
• Language: croatian
• URN:NBN: urn:nbn:hr:217:942141
• Promotion: 2022
• 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: Doctoral study in chemistry; Study programme type: university; Study level: postgraduate; Academic / professional title: doktor/doktorica znanosti, područje prirodnih znanosti, polje kemija (doktor/doktorica znanosti, područje prirodnih znanosti, polje kemija)
• Type of resource: Text
• Extent: 178 str. ; 30 cm
• File origin: Born digital
• Access conditions: Open access; Embargo expiration date: 2022-12-14
• Created on: 2022-06-20 13:31:52