Preparation and characterization of a benzyl-, benzo-3,4-(1,3-dioxolyl)-, methyl-thiophene-2-carboxylate-3-yl, 2-naphthyl-, and p-trifluoromethoxy-phenyl-macrozone, new conjugates of macrolide antibiotics

Makrolidni antibiotici, kao što je azitromicin, imaju široku primjenu u liječenju infekcija dišnih puteva. Djeluju kao inhibitori sinteze proteina vežući se na bakterijsku ribosomsku podjedinicu 50S. Zbog povećane rezistencije bakterija javlja se potreba za razvojem novih, poboljšanih antibiotika. Dobru antibakterijsku aktivnost in vitro na odabrane Gram-pozitivne i Gram-negativne bakterije pokazuju makrozoni, novi konjugati azitromicina i tiosemikarbazida. Konjugacijom 9a-(γ-aminopropil) derivata azitromicina i novosintetiziranih tiosemikarbazida e1-e5 pripravljeno je pet novih spojeva, f1-f5. Sintetizirani spojevi pročišćeni su kolonskom kromatografijom, a struktura im je određena na temelju snimljenih jedno- i dvodimenzijskih spektara NMR te spektara MS. Budućim istraživanjima ispitat će se biološka aktivnost pripravljenih spojeva. Macrolide antibiotics, such as azithromycin, have been widely prescribed for the treatment of respiratory tract infections. They act as inhibitors of protein synthesis by binding to the bacterial ribosomal subunit 50S. Drug resistant microbial pathogens today represent a serious global problem that requires the discovery of new and more effective antimicrobial agents. Macrozones are novel conjugates of azithromycin and thiosemicarbazides that shows very good antibacterial activity. Five new compounds f1-f5 were prepared by conjugation of the 9a-(γ-aminopropil) azithromycin derivative and the newly synthesized thiosemicarbazides e1-e5. The synthesized compounds were purified by column chromatography. The structures of novel macrozones were proposed on the basis of recorded one- and two-dimensional NMR spectra and the MS spectra, respectively.