Antimicrobial and antitumor activity of peptidomimetics synthesized from amino acids.

• Peptidomimetics with an alkyl substituent were synthesized from amino acids. • The peptidomimetics exhibit broad-spectrum and efficient antibacterial properties. • The peptidomimetics have the potential to combat drug-resistant bacteria. • The peptidomimetics showed good antitumor activity and low cytotoxicity. Thirteen cationic peptidomimetics derived from amino acids bearing an alkyl or ethynylphenyl moiety that mimic the structure of cationic antibacterial peptides were designed and synthesized using a simple coupling reaction of an amino acid with a substituted amine. Antibacterial activities of the resulting peptidomimetics against drug-sensitive bacteria, such as Gram-positive Staphylococcus aureus (S. aureus) and Bacillus subtilis , Gram-negative Escherichia coli (E. coli) and Salmonella enterica , and a drug-resistant bacterium, methicillin-resistant S. aureus (MRSA), were systematically evaluated. Most peptidomimetics show significant broad-spectrum antibacterial activity. A-L-Iso-C 12 (isoleucine derivative bearing a dodecyl moiety) show MICs of 2.5 μg/mL against S. aureus and 4 μg/mL against MRSA and A-L-Val-C 12 (valine derivative bearing a dodecyl moiety) show MICs of 1.67 μg/mL against E. coli and 8.3 μg/mL against MRSA. A-L-Val-C 12 showed low cytotoxicity toward L929 cells in comparison with SGC 7901 cells, indicating tumor-directed killing by peptidomimetics while avoiding toxicity to normal cells. The influences of type of amino acid and substituent, length of substituent, and stereochemistry of amino acids on antibacterial activity and cytotoxicity of peptidomimetics were systematically investigated. The results indicate that this series of cationic peptidomimetics derived from amino acids display antitumor activity and may be useful for treatment of bacterial infections. [ABSTRACT FROM AUTHOR]