| Popis: |
Makrolidni antibiotici pripadaju skupni makrolida koji se široko primjenjuju za liječenje infekcija gornjih i donjih dišnih puteva. Mehanizam djelovanja makrolida temelji se na vezanju za 23S rRNA u peptidil-transferaznom centru bakterijskog ribosoma ili u njegovoj blizini, što sprječava izlaz novosintetiziranih peptida i inhibira sintezu proteina. Pojava višestruke bakterijske rezistencije predstavlja ozbiljnu prijetnju za ljudsko zdravlje, što je potaknulo sintezu novih derivata makrolida koji će pokazivati bolju bioaktivnost. Vezanjem poznatih makrolida i bioaktivnih tiosemikarbazona dobiveni su novi konjugati, makrozoni, koji uspješno djeluju protiv nekih rezistentnih bakterijskih sojeva. U ovom radu okarakterizirane su interakcije nekoliko 4''-aril-makrozona s biološkim metama, poput albumina iz goveđeg seruma te ribosoma iz bakterije Escherichia coli. Istraživanja su provedena kombinacijom metoda spektrofluorimetrije, spektrofotometrije i cirkularnog dikroizma. Kao kompetitor u fluorimetrijskim mjerenjima korišten je flourescirajući derivat azitromicina, 9a-NBD-azitromicin. Podaci su zatim obrađeni metodama multivarijatne analize kako bi se odredile konstante vezanja. Due to their anti-infective activity, macrolide antibiotics (macrolides) are widely used for the treatment of upper and lower respiratory tract infections. Their mechanism of action is based on reversible binding to 23S rRNA at or near the peptidyl-transferase center of the bacterial ribosome, which prevents the release of newly synthesized peptides and inhibits the protein synthesis. The emergence of bacterial resistance represents a serious threat to human health, which prompted the synthesis of new macrolide derivatives with a better bioactivity. Linking known macrolides to bioactive thiosemicarbazones resulted with new conjugates, macrozones, active against some resistant bacterial strains. In this work, the interactions of several 4''-aryl-macrozones with biological targets, such as bovine serum albumin and Escherichia coli ribosomes, were characterized. The studies were carried out by combining spectrofluorimetric, spectrophotometric and circular dichroism methods. Competition fluorimetric experiments were conducted using a fluorescent derivative of azithromycin, 9a-NBD-azithromycin. The data were further processed with multivariate analysis methods to determine the binding constants. |
