title: Synthesis, Antibacterial, and Anticancer Evaluation of Novel Spiramycin-Like Conjugates Containing C(5) Triazole Arm.
abstract: Huisgen cycloaddition allowed obtaining of novel triazole-bridged antibiotics (6-16) with the reconstructed C(5) arm of spiramycin. (1)H-(1)H NOESY couplings indicated the structure of novel derivatives in solution and demonstrated that the rebuilt C(5) arm is slightly differently oriented relative to the aglycone part if compared to that of spiramycin (1). Combined analysis of biological data together with experimentally determined lipophilicity (clogP) and solubility show the importance of the chemical nature of the newly introduced triazole C(5) arm in the presence of attractive antibacterial and anticancer potency. The most cytotoxic active triazole conjugates having a hydrophobic and bulky C(5) arm showed higher selectivity toward cancer cell lines (HeLa, KB, MCF-7, Hep-G2, and U87) relative to HDF normal cells than that of the parent spiramycin. Our studies have demonstrated that the aldehyde group is not crucial for the presence of interesting antibacterial [MIC(S. pneumoniae) ∼ 1.2 μM] and anticancer [IC50(HepG2) ∼ 6 μM] properties of 16-membered lactone macrolides based on spiramycin's aglycone.
authors: Faculty of Chemistry, Adam Mickiewicz University , Umultowska 89b, 61-614 Poznan, Poland.
authors: Katarzyna
authors: K
authors: Klich
authors: Faculty of Chemistry, Adam Mickiewicz University , Umultowska 89b, 61-614 Poznan, Poland.
authors: Krystian
authors: K
authors: Pyta
authors: Department of Genetics and Pharmaceutical Microbiology, University of Medical Sciences , Swiecickiego 4, 60-781 Poznan, Poland.
authors: Marcelina M
authors: MM
authors: Kubicka
authors: Department of Pharmacology, University of Medical Sciences , Rokietnicka 5a, 60-806 Poznan, Poland.
authors: Piotr
authors: P
authors: Ruszkowski
authors: Faculty of Chemistry, Adam Mickiewicz University , Umultowska 89b, 61-614 Poznan, Poland.
authors: Lech
authors: L
authors: Celewicz
authors: Department of Genetics and Pharmaceutical Microbiology, University of Medical Sciences , Swiecickiego 4, 60-781 Poznan, Poland.|Institute of Human Genetics, Polish Academy of Sciences , Strzeszynska 32, 60-479 Poznan, Poland.
authors: Marzena
authors: M
authors: Gajecka
authors: Faculty of Chemistry, Adam Mickiewicz University , Umultowska 89b, 61-614 Poznan, Poland.
authors: Piotr
authors: P
authors: Przybylski
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D045744:Cell Line, Tumor; D061565:Cycloaddition Reaction; D004354:Drug Screening Assays, Antitumor; D006094:Gram-Positive Bacteria / Q000187:drug effects; D006801:Humans; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D012995:Solubility; D015572:Spiramycin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013816:Thermodynamics; D014230:Triazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D000970:Antineoplastic Agents; D014230:Triazoles; D015572:Spiramycin