Efficient synthesis and biological evaluation of proximicins A, B and C.

TitleEfficient synthesis and biological evaluation of proximicins A, B and C.
Publication TypeJournal Article
Year of Publication2012
AuthorsBrucoli F, Natoli A, Marimuthu P, Borrello MTeresa, Stapleton P, Gibbons S, Schätzlein A
JournalBioorg Med Chem
Date Published2012 Mar 15
KeywordsAnti-Bacterial Agents, Antibiotics, Antineoplastic, Apoptosis, Bacterial Infections, Cell Line, Tumor, Enterococcus faecalis, Escherichia coli, Female, Humans, Methicillin-Resistant Staphylococcus aureus, Microbial Sensitivity Tests, Neoplasms, Netropsin, Staphylococcus aureus

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.

Alternate JournalBioorg. Med. Chem.
PubMed ID22364744