title: Efficient synthesis and biological evaluation of proximicins A, B and C.
abstract: A quick and efficient synthesis and the biological evaluation of promising antitumor-antibiotics proximicins A, B and C are reported. The characteristic repetitive unit of these molecules, the methyl 4-Boc-aminofuran-2-carboxylate 15, was prepared in three synthetic steps in good yield using an optimised copper-catalysed amidation method. The proximicins were evaluated for their antitumor activity using cellular methods. Proximicin B induced apoptosis in both Hodgkin's lymphoma and T-cell leukemia cell lines and proximicin C exhibited significantly high cytotoxicity against glioblastoma and breast carcinoma cells. The proximicins were also screened against Escherichia coli, Enterococcus faecalis and several strains of methicillin-and multidrug-resistant Staphylococcus aureus. Proximicin B showed noteworthy activity against antibiotic-resistant Gram-positive cocci.
authors.affiliation: UCL School of Pharmacy, 29-39 Brunswick Square, London, WC1N 1AX, UK. federico.brucoli@pharmacy.ac.uk
authors.forename: Federico
authors.initials: F
authors.lastname: Brucoli
authors.forename: Antonino
authors.initials: A
authors.lastname: Natoli
authors.forename: Preethi
authors.initials: P
authors.lastname: Marimuthu
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Borrello
authors.forename: Paul
authors.initials: P
authors.lastname: Stapleton
authors.forename: Simon
authors.initials: S
authors.lastname: Gibbons
authors.forename: Andreas
authors.initials: A
authors.lastname: Schätzlein
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D000903:Antibiotics, Antineoplastic / Q000138:chemical synthesis* / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001424:Bacterial Infections / Q000188:drug therapy; D045744:Cell Line, Tumor; D013293:Enterococcus faecalis / Q000187:drug effects; D004926:Escherichia coli / Q000187:drug effects; D005260:Female; D006801:Humans; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D009369:Neoplasms / Q000188:drug therapy; D009429:Netropsin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology*; D013211:Staphylococcus aureus / Q000187:drug effects
chemical_list: D000900:Anti-Bacterial Agents; D000903:Antibiotics, Antineoplastic; C529559:proximicin A; C529560:proximicin B; C529561:proximicin C; D009429:Netropsin