Sinteza i karakterizacija 9a-N-aminopropil i 4''-O-aminopropil derivata azitromicina

master's thesis

• Title (english): Synthesis and characterization of 9a-N-aminopropyl and 4''-O-aminopropyl derivatives of azithromycin
• Author: Marko Horvat
• Mentor: Predrag Novak (mentor)
• Mentor: Mirjana Bukvić (mentor)
• Committee member: Predrag Novak (predsjednik povjerenstva)
• Committee member: Mirta Rubčić (član povjerenstva)
• Committee member: Đani Škalamera (član povjerenstva)
• Committee member: Tomislav Jednačak (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Chemistry); Zagreb
• Defense date and country: 2022-09-29, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Chemistry

Abstract

Makrolidni antibiotici, kao što je azitromicin, imaju široku primjenu u liječenju infekcija dišnih
puteva uzrokovanih Gram-pozitivnim i Gram-negativnim bakterijama. Tiosemikarbazoni, kao
i neki njihovi metalni kompleksi, također pokazuju antibiotsku, protuupalnu i antitumorsku
aktivnost. Racionalnim pristupom u spajanju ovih dviju klasa spojeva moguće je dobiti novu
klasu makrolidnih konjugata „makrozona“, s poboljšanom biološkom aktivnošću, ujedno
aktivnim i na rezistentne bakterijske sojeve. Stoga su sintetizirani novi biološki aktivni
konjugati makrolidnih antibiotika dobivenih vezanjem različitih tiosemikarbazonskih derivata
na 9a-N i 4''-O γ-aminopropil-azitromicin uz izolaciju putem preparativnog LC-MS-a i njihovu
karakterizaciju pomoću 1D i 2D NMR-a. Pripravljenim spojevima ispitano je antimikrobno
djelovanje na niz osjetljivih i rezistentnih sojeva Gram-pozitivnih (Staphylococcus aureus,
Streptococcus pneumoniae, Enterococcus faecalis, Streptococcus pyogenes) i Gram-negativnih
bakterija (Escherichia coli, Moraxella catarrhalis) ključnim za područje djelovanja
makrolidnih antibiotika.

Abstract (english)

Macrolide antibiotics, such as azithromycin, have wide application in the treatment of
respiratory infections caused by Gram-positive and Gram-negative bacteria.
Thiosemicarbazones, as well as some of their metal complexes, also show antibiotic, antiinflammatory and antitumor activity. With a rational approach in combining these two classes
of compounds, it is possible to obtain a new class of macrolide conjugates "macrozones", with
improved biological activity, while also active in resistant bacterial strains. Thus, new
biologically active conjugates of macrolide antibiotics obtained by binding various
thiosemicarbazone derivatives to 9a-N and 4''-O γ-aminopropyl-azithromycin were synthesized
with isolation by preparative LC-MS and their characterization by 1D and 2D NMR. The
prepared compounds were tested for antimicrobial activity on a number of sensitive and
resistant strains of Gram-positive (Staphylococcus aureus, Streptococcus pneumoniae,
Enterococcus faecalis, Streptococcus pyogenes) and Gram-negative bacteria (Escherichia coli
and Moraxella catarrhalis) which are crucial for the area of application of macrolide antibiotics

• Keywords: antibiotici; azitromicin; ispitivanje in vitro; makrozoni; rezistencija; tiosemikarbazoni
• Keywords (english): antibiotics; azithromycin; in vitro evaluation; macrozone; resistance; thiosemicarbazone
• Language: croatian
• URN:NBN: urn:nbn:hr:217:157902
• 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: Open access
• Created on: 2022-10-12 09:38:17