Bioorganic & Medicinal Chemistry 2012-03-15

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

Federico Brucoli, Antonino Natoli, Preethi Marimuthu, Maria Teresa Borrello, Paul Stapleton, Simon Gibbons, Andreas Schätzlein

Index: Bioorg. Med. Chem. 20 , 2019-24, (2012)

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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.Copyright © 2012 Elsevier Ltd. All rights reserved.