Synthesis of new analogues of the siderophore piscibactin

master's thesis

• Title (croatian): Sinteza novih analoga siderofora piscibactina
• Author: Karlo Andlovec
• Mentor: Valerije Vrček (mentor)
• Mentor: Jaime Rodriguez Gonzalez https://orcid.org/0000-0002-4143-883X (mentor)
• Committee member: Valerije Vrček (predsjednik povjerenstva)
• Committee member: Ivana Perković (član povjerenstva)
• Committee member: Davor Šakić (član povjerenstva)
• Granter: University of Zagreb; Faculty of Pharmacy and Biochemistry; (Department of organic chemistry); Zagreb
• Defense date and country: 2024-09-27, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Pharmacy; Pharmacy

Abstract

Rastući broj bakterijskih oboljenja u riba negativno utječe na sektor ribarstva i akvakulture.
Antimikrobna rezistencija postaje jedan od najzabrinjavajućih problema u zdravstvenom sektoru
diljem svijeta, rezultirajući hitnom potrebom za implementacijom novih strategija kako bi se zarazne
bolesti prevenirale i zaustavile. Javlja se i potreba za izumom djelotvornih antibiotika koji bi
pomogli u borbi protiv rezistencije među bakterijama. Piscibactin (Pcb) je siderofor fenolnog tipa
koji se sastoji od dva tiazolinska i jednog tiazolidinskog prstena. Olakšava unos Fe3+ iona u bakterije
kao što su Photobacterium damselae subsp. piscicida i Vibrio anguillarum. Međutim, ograničena
stabilnost narušava potencijalnu primjenu u medicinske i biotehnološke svrhe. Stoga je razvoj
stabilnih Pcb analoga ključan za daljnji napredak. Ovaj rad izlaže sintetski put pojednostavljenog
Pcb analoga s promijenjenim strukturnim značajkama, uzevši u obzir računske rezultate. Oksazoloksazolin-
tiazol intermedijer analoga piscibactina uspješno je sintetiziran i mogao bi služiti kao
napredni intermedijer u budućoj sintezi analoga, kao i u farmaceutskoj industriji. Svi sintetizirani
spojevi karakterizirani su pomoću tehnika NMR-a i masene spektrometrije.

Abstract (english)

The fishery and aquaculture sector are being negatively impacted by a rising number of bacterial
diseases in fish. Additionally, antimicrobial resistance is becoming one of the most concerning
problems in the health sector globally. As a result, there is an urgent need of implementing new
strategies to prevent and stop infectious diseases, as well as inventing effective antibiotics, which
would help fight the resistance amongst bacteria. Piscibactin (Pcb) is a phenolate-type siderophore,
comprising two thiazoline and one thiazolidine rings. It facilitates Fe3+ ion uptake in bacteria, such
as Photobacterium damselae subsp. piscicida and Vibrio anguillarum. However, its limited stability
impairs the potential medical and biotechnological applications. Therefore, the development of
stable Pcb analogues is crucial for further advancement. This study proposes the design of a
simplified analogue of Pcb with alternative structural features, guided by computational results. The
oxazole-oxazoline-thiazole Pcb analogue intermediate was successfully synthesised, and it could be
used as an advanced intermediate in further analogue synthesis, as well as in pharmaceutical
industry. All the synthesised compounds were characterised by both NMR and mass spectrometry
techniques.

• Keywords: piscibactin; siderofor; O_OZ_T analog; računalni izračuni
• Keywords (english): piscibactin; siderophore; O_OZ_T analogue; computational calculations
• Language: croatian
• URN:NBN: urn:nbn:hr:163:167128
• Study programme: Title: Pharmacy - integrated undergraduate and graduate - university study; Study programme type: university; Study level: integrated undergraduate and graduate; Academic / professional title: sveučilišni magistar farmacije (sveučilišni magistar farmacije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2025-01-10 11:48:32