Antimikrobni učinak željezovih i galijevih kompleksa aroilhidrazona u in vitro uvjetima

master's thesis

• Title (english): In vitro antimicrobial activity of aroylhydrazone complexes with iron and gallium
• Author: Dražen Lež
• Mentor: Ivan Kosalec (mentor)
• Committee member: Ivan Kosalec (predsjednik povjerenstva)
• Committee member: Ana Budimir (član povjerenstva)
• Committee member: Lidija Bach-Rojecky (član povjerenstva)
• Granter: University of Zagreb; Faculty of Pharmacy and Biochemistry; (Department of microbiology); Zagreb
• Defense date and country: 2020-09-10, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Pharmacy; Pharmacy

Abstract

Mikrobni metabolizam željeza predstavlja dobru metu za antibakterijsko i antifungalno djelovanje. Metal galij zbog svojih sličnosti sa željezom i nemogućnosti bioloških sustava da ih razlikuju potencijalni je inhibitor metaboličkih puteva ovisnih o željezu. Koncept „trojanskog konja“ podrazumijeva upotrebu antimikrobnih tvari koje mikroorganizmi smatraju izvorima željeza te ih aktivno unose u stanicu. Primjeri takvih spojeva su hidrazoni i aroilhidrazoni, tvari s poznatim antimikrobnim učincima koje su ujedno i kelatori željeza, odnosno galija. Kompleksi hidrazona i galija stabilniji su i bolje bioraspoloživosti od samog galija, a ujedno predstavljaju kombinaciju dviju tvari s poznatim antimikrobnim učinkom u jednom spoju. Od trinaest novosintetiziranih kompleksa aroilhidrazona (izvedenih iz salicilaldehida i hidrazida nikotinske kiseline) sa željezom i galijem, metodom difuzije u agaru ustanovljeno je da samo kompleksi s galijem pokazuju antimikrobni učinak u in vitro uvjetima na ispitanim sojevima S. aureus, E. coli i C. albicans. Metodom mikrodilucije određene su IC50 i IC90 (MIK) vrijednosti spojeva 1 – 13. Najbolju aktivnost pokazuju spoj 5 (MIK iznosi 59,60 μg/mL za E. coli ATCC 10536 i 111,2 μg/mL za ESBL+ E. coli MFBF 12794), spoj 6 (MIK iznosi 32,02 μg/mL za C. albicans ATCC 10231 i 64,62 μg/mL za C. albicansFLR+ MFBF 11100) i spoj 7 (MIK iznosi 97,95 μg/mL za S. aureus ATCC 6538 i 109,1 μg/mL za MRSA MFBF 177). „Time-kill“ metodom utvrđeno je da spoj 6 pokazuje fungistatski učinak u koncentraciji 2xMIK tijekom 24 sata na sojevima C. albicans ATCC 10231 i C. albicansFLR+ MFBF 11100 u in vitro uvjetima. Isti kompleks doveo je do 26,80% redukcije logaritma stanične vijabilnosti C. albicans ATCC, odnosno 30,12 % redukcije kod C. albicansFLR+ nakon 24 sata inkubacije.

Abstract (english)

Iron metabolism of microorganisms represents a good target for antibacterial and antifungal treatment. Because of its similarities with iron and disability of biological systems to differentiate them, metal gallium is a potential inhibitor of iron-dependent metabolic pathways. A „Trojan Horse“ concept implies using antimicrobial agents which microorganisms consider as iron source and they actively transport them inside a cell. Example of such compounds are hydrazones and aroylhydrazones, substances with known antimicrobial activity and ability to chelate iron and gallium. Gallium and hydrazone complexes are more stable and more bioavailabilable than gallium itself. At the same time, they represent a combination of two substances with known antimicrobial acitivity in one compound. Of thirteen newly synthesized aroylhydrazone complexes (derived from salicyaldehide and nicotinic acid hydrazide) with iron and gallium, only gallium complexes showed in vitro antimicrobial activity on tested S. aureus, E. coli and C. albicans strains when using agar-well diffusion method. IC50 and IC90 (MIC) values were determined with broth dilution for compuonds 1 – 13. Compuond 5 (MIC equals 59,60 μg/mL for E. coli ATCC 10536 and 111,2 μg/mL for ESBL+ E. coli MFBF 12794), compound 6 (MIC equals 32,02 μg/mL for C. albicans ATCC 10231 and 64,62 μg/mL for C. albicansFLR+ MFBF 11100) and compund 7 (MIC equals 97,95 μg/mL for S. aureus ATCC 6538 and 109,1 μg/mL for MRSA MFBF 177) showed the best activity. „Time-kill“ assay showed that compound 6 expresses fungistatic activity at 2xMIC concentration during 24 hours on C. albicans ATCC 10231 and C. albicansFLR+ MFBF 11100 strains in vitro. Same complex reduced the logarithm of C. albicans ATCC cellular viability by 26,80% and C. albicansFLR+ viability by 30,12% after 24 hours incubation.

• Keywords: aroilhidrazoni; željezo; galij; S. aureus; E. coli; C. albicans
• Keywords (english): aroylhydrazones; iron; gallium; S. aureus; E. coli; C. albicans
• Language: croatian
• URN:NBN: urn:nbn:hr:163:493511
• Study programme: Title: Pharmacy; Study programme type: university; Study level: integrated undergraduate and graduate; Academic / professional title: magistar/magistra farmacije (magistar/magistra farmacije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2021-04-28 10:28:52