Acta Pharm. 55 (2005) 387-399

Antimicrobial activity of N-phthaloylamino acid hydroxamates

JULIJA MATIJEVIC-SOSA^1* and ZDENKA CVETNIC²

jmatijevic@pharma.hr

¹Department of Biochemistry and Molecular Biology, Faculty of Pharmacy and Biochemistry, University of Zagreb, Zagreb, Croatia
²Department of Microbiology, Faculty of Pharmacy and Biochemistry, University of Zagreb, Zagreb, Croatia

Antibacterial and antifungal activity of N-phthaloylamino acid hydroxamates 1-3 /C₆H₄(CO)₂N-x-CONHOH, x = amino acid residues of glycine, ß-alanine and D-phenylglycine/ was examined against 44 strains of Gram-positive and Gram-negative bacteria, and 10 species of yeasts. The level of antimicrobial effects was established using the in vitro agar assay and the standard broth dilution susceptibility test. N-phthaloyl-D-phenylglycine-hydroxamic acid (3), the substance with the highest lipophilicity (log P), showed the best antibacterial activity, especially against Gram-negative bacteria. Minimum inhibitory concentration of 3 was 0.008 mg mL^-1 in the activity against Yersinia enterocolitica O3, confirmed by a large inhibition zone (30 mm) by the diffusion test. Hydroxamates inhibit growth by chelation of PDF enzyme metal in both Gram-positive and Gram-negative bacteria, and LpxC enzyme in Gram-negative enzyme. Phthalimides apear to contribute to inhibition by destabilizing m-RNA. Antifungal activity of substances 1-3 is not very expressed.

Keywords: hydroxamic acid, phthalimide, antibacterial activity, lipophilicity