Novel Antibiotics for the Treatment of Gram-Positive Bacterial Infections

Abstract
The natural dipeptide antibiotic TAN 1057 A,B displays excellent antibacterial activity against staphylococci including methicillin resistant Staphylococcus aureus. However, the in vitro activity against additional Gram-positive strains, in particular pneumococci and Enterococcus faecalis, proved to be considerably lower. We report the synthesis and pharmacological evaluation of new derivatives of this natural product that displayed increased antibacterial potency against staphylococci and were also active against pneumococci. In particular, the analogues bearing modified β-homoarginine side chains with methylated guanidine moieties were shown to be significantly more potent than the natural product TAN 1057 A,B.