Priprava i karakterizacija novih 4”-derivata azitromicina: 4-piperidil-sulfonilfenil-, 3-piridil-, benzo-3,4-(1,3-dioksolil)-, etoksikarbonil-, metiltiofen-2-karboksilat-3-il- i 2-furfurilmetil-makrozona

master's thesis

• Title (english): Synthesis and characterization of new 4"-azithromycin derivatives: 4-piperidyl-sulfonylphenyl-, 3-pyridyl-, benzo-3,4-(1,3-dioxolyl)-, ethoxycarbonyl-, methyltiophene-2-carboxylate-3-yl- and 2-furfurylmethyl-macrozones
• Author: Antonio Barišić
• Mentor: Predrag Novak (mentor)
• Committee member: Predrag Novak (predsjednik povjerenstva)
• Committee member: Đani Škalamera (član povjerenstva)
• Committee member: Željka Soldin (član povjerenstva)
• Committee member: Sanda Rončević (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Chemistry); Zagreb
• Defense date and country: 2020-02-26, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Chemistry

Abstract

Makrolidni antibiotici (npr. azitromicin) imaju široku primjenu u liječenju infekcija uzrokovanih Gram-pozitivnim, Gram-negativnim bakterijama i nekim unutarstaničnim organizmima, te su ujedno pokazali antiupalno i antikancerogeno djelovanje. Djeluju na principu inhibicije sinteze bakterijskog proteina vežući se na 50S podjedinicu bakterijskog ribosoma. S obzirom na sve bržu prilagodbu bakterija i njihovu rezistenciju na makrolidne antibiotike, javlja se potreba za novim spojevima koji će pokazati veću biološku aktivnost. Osim makrolida, dobru antibakterijsku aktivnost su pokazali i tiosemikarbazoni. Makrozoni predstavljaju nove konjugate derivata azitromicina i tiosemikarbazona. U ovom radu uspješno je pripravljeno pet makrozona reakcijom 4"-aminopropilnog derivata azitromicina i odgovarajućih tiosemikarbazona. Derivat azitromicina pročišćen je kromatografijom na stupcu, a makrozoni tehnikom LC-SPE i semipreparativnom tekućinskom kromatografijom. Pripravljeni i pročišćeni makrozoni okarakterizirani su: spektrometrijom mase, spektroskopijom NMR i tekućinskom kromatografijom visoke djelotvornosti. Idući korak istraživanja uključit će in vitro testove biološke aktivnosti pripravljenih makrozona na susceptibilne i rezistentne sojeve bakterija.

Abstract (english)

Macrolide antibiotics (e.g. azithromycin) are widely used in the treatment of infectious deseases caused by Gram-positive and Gram-negative bacteria and some intracellular organisms. They have also shown anti-inflammatory and anticancer activities. Macrolides exert their activity by binding to the 50S subunit of the bacterial ribosome thus inhibiting bacterial protein synthesis. Owing to the fact that bacteria develop resistance to existing antibiotics, new chemical entities are urgently needed to fight resistance mechanisms. Thiosemicarbazones have also shown good antibacterial activity. Hence, we believe that conjugation of azithromycin and thiosemicarbazones could yield a novel class of bioactive compounds, the macrozones. Here we report synthesis and characterization of five macrozones by reaction of 4“-aminopropyl azithromycin and the corresponding thiosemicarbazones. All prepared compounds were purified by column and semipreparative liquid chromatography and LC-SPE system. The next step of the study will include in vitro biological evaluation against a panel of susceptible and resistant bacteria strains.

• Keywords: azitromicin; makrolid; makrozon; tiosemikarbazon; tiosemikarbazid; spektroskopija NMR
• Keywords (english): azithromycin; macrolide; macrozone; thiosemicarbazone; thiosemicarbazide; spectroscopy NMR
• Language: croatian
• URN:NBN: urn:nbn:hr:217:491171
• 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; Embargo expiration date: 2021-02-26
• Created on: 2020-07-20 09:19:30