Discovery of novel ureas and thioureas of 3-decladinosyl-3-hydroxy 15-membered azalides active against efflux-mediated resistant Streptococcus pneumoniae |
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Authors: | Bukvić Krajačić Mirjana Dumić Miljenko Novak Predrag Cindrić Mario Koštrun Sanja Fajdetić Andrea Alihodžić Sulejman Brajša Karmen Kujundžić Nedjeljko |
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Affiliation: | a GlaxoSmithKline Research Centre Zagreb, Prilaz baruna Filipovi?a 29, HR-10000 Zagreb, Croatia b Department of Biotechnology, University of Rijeka, S. Krautzeka bb, HR-51000 Rijeka, Croatia c Department of Chemistry, Faculty of Science, University of Zagreb, Horvatovac 102a, HR-10000 Zagreb, Croatia d Institute ‘Ru?er Boškovi?’, Bijeni?ka cesta 54, HR-10000 Zagreb, Croatia |
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Abstract: | A series of novel ureas and thioureas of 3-decladinosyl-3-hydroxy 15-membered azalides, were discovered, structurally characterized and biologically evaluated. They have shown good antibacterial activity against selected Gram-positive and Gram-negative bacterial strains. These include N″ substituted 9a-(N′-carbamoyl-γ-aminopropyl)- (6a,c), 9a-(N′-thiocarbamoyl-γ-aminopropyl)- (7a,e), 9a-[N′-(β-cyanoethyl)-N′-(carbamoyl-γ-aminopropyl)]- (9a-c, 9g) 9a-[N′-(β-cyanoethyl)-N′-(thiocarbamoyl-γ-aminopropyl)]-derivatives (10d-f) of 5-O-desosaminyl-9-deoxo-9-dihydro-9a-aza-9a-homoerythronolide A (3).Among the synthesized compounds thiourea 7a and urea 9b have shown substantially improved activity comparable to azithromycin (1) and significantly better activity than the 3-decladinosyl-azithromycin (2) and the parent 3-cladinosyl analogues against efflux-mediated resistant S. pneumoniae. |
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Keywords: | Azalides 3-Decladinosyl Ureas Thioureas Synthesis Antibacterial activity |
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