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Antimicrobial susceptibility testing of anaerobic bacteria for amidine derivatives of 3,4-ethylenedioxytiophene

By Sara Lipovac

Abstract

Pojava i kontinuirano širenje bakterijske rezistencije na klinički značajne antibiotike sve više ugrožava učinkovitu terapiju brojnih zaraznih bolesti te predstavlja veliki javnozdravstveni problem. Razumijevanje mehanizama otpornosti od velike je važnosti kako za učinkovitu antimikrobnu terapiju, tako i za razvoj novih antimikrobnih lijekova. U ovom radu ispitivana je antibakterijska aktivnost amidinskih derivata 3,4-etilendioksitiofena na anaerobnim bakterijskim sojevima. Navedeni spojevi predstavljaju novu klasu kemijskih entiteta koji se vežu za molekulu DNA u malom utoru dvostruke zavojnice i remete njeno normalno funkcioniranje. Ukupno osam derivata testirano je dvjema različitim metodama – metodom mikrodilucije i metodom agar dilucije. Rezultati mikrodilucijske metode pokazali su kako su bis-fenilni derivati s razgranatim supstituentima vezanim na terminalne amidinske skupine (spojevi 23 i 24) najpotentniji i imaju najširi spektar djelovanja. Preostala dva bis-fenila s nerazgranatim amidinom ili izopropilom kao supstituentom (spojevi 21 i 22) i ostale tri podskupine testiranih spojeva, asimetrični derivati (spojevi 10 i 11), bis-benzimidazol (spoj 19) i bis-karboksamidofenili (spoj 27), uglavnom su pokazali slabiju antibakterijsku aktivnost u odnosu na spojeve 23 i 24. Metodom agar dilucije umjerenu antibakterijsku aktivnost, osim na Bacteroides i Lactobacillus vrste koje su bile neosjetljive, pokazali su spojevi 22 – 24. Sve bakterijske vrste bile su neosjetljive na preostalih pet spojeva. Budući da se rezultati dobiveni dvjema metodama međusobno razlikuju treba ih interpretirati s oprezom te dodatno utvrditi razloge uočenih nepodudarnosti.The development and constant increase of antibiotic resistance has become a global health problem which is threatening the effective therapy of numerous infectious diseases. Understanding the mechanisms of resistance has a crucial impact on both choosing effective antibiotic treatment and design of new antimicrobial agents. The aim of this thesis was to assessed antimicrobial activity of amidine derivatives of 3,4-ethylenedioxytiophene in different anaerobic bacterial strains. These new chemical entities represent a novel class of antibacterial compounds, so called minor groove binders (MGBs). They inhibit DNA function and RNA sythesis in bacteria by binding to duplex DNA in the minor groove. Eight derivatives in total were tested by two different susceptibility testing methods – microdilution and agar dilution. The results of microdilution testing showed that two bis-phenyl derivatives with alkyl end groups (compounds 23 and 24) are the most active and have the best overall antibacterial activity. The other two bis-phenyl compounds (21 i 22), as well as other subclasses of derivatives, asimetrical compounds (10 i 11), bis-benzimidazole (19) and carboxamid-amidine (27) show, in general, lower antimicrobial activitiy compared to compounds 23 and 24. Agar dilution method revealed that compounds 22 – 24 have moderate activity on anaerobes (except Bacteroides and Lactobacillus strains which appeared insensitive). All bacterial strains are insensitive to remaining tested compounds. Since the results obtained by two different methods do not completely correlate, these findings should be critically revised and further investigations are recomended to explain the observed differences

Topics: amidinski derivati 3, 4-etilendioksitiofena, antimikrobni lijekovi, anaerobne bakterije, agar dilucija, mikrodilucija, amidine derivatives of 3, 4-ethylenedioxythiophene, antimicrobial agents, anaerobic bacteria, microdilution, agar dilution, BIOMEDICINA I ZDRAVSTVO. Farmacija. Farmacija., BIOMEDICINE AND HEALTHCARE. Pharmacy. Pharmacy.
Publisher: University of Zagreb. Faculty of Pharmacy and Biochemistry. Department of medical biochemistry and haematology.
Year: 2016
OAI identifier: oai:repozitorij.unizg.hr:pharma_354
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