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In this communication, we report the design, synthesis and in vitro antimicrobial activity of ultra short peptidomimetics. Besides producing promising antibacterial activities against Staphylococcus aureus and methicillin-resistant S. aureus (MRSA), the dipeptidomimetics exhibited high antifungal activity against C. neoformans with IC 50 values in the range of 0.16-19 μg/mL. The most potent analogs exhibited 4-fold higher activity than the currently used drug amphotericin B, with no apparent cytotoxicity in a panel of mammalian cell lines.

Synthesis and antimicrobial activities of His(2-aryl)-Arg and Trp-His(2-aryl) classes of dipeptidomimetics