Antimicrobial activity of N-phthaloylamino acid hydroxamates.
Antibacterial and antifungal activity of N-phthaloylamino acid hydroxamates [C6H4(CO)2N-X-CONHOH, X=amino acid residues of glycine, beta-alanine or D-phenylglycine], was examined against 44 strains of Gram-positive and Gram-negative bacteria, and 10 species of yeasts. The level of antimicrobial activity was established using the in vitro agar assay and the standard broth dilution susceptibility test. N-phthaloyl-D-phenylglycine-hydroxa- mic acid , the substance with the highest lipophilicity (log P), showed the best antibacterial activity, especially against Gram-negative bacteria. Minimum inhibitory concentration of 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 the PDF enzyme metal in both Gram-positive and Gram-negative bacteria, and LpxC enzyme in Gram-negative enzyme. Phthalimides appear to contribute to inhibition by destabilizing m-RNA. Antifungal activity of substances is not very expressed.
Matijević-Sosa
Julija
J
Department of Biochemistry and Molecular Biology, Faculty of Pharmacy and Biochemistry, University of Zagreb, Croatia. jmatijevic@pharma.hr
Cvetnić
Zdenka
Z
D000581:Amidohydrolases / Q000037:antagonists & inhibitors / Q000378:metabolism; D000626:Aminopeptidases / Q000037:antagonists & inhibitors / Q000378:metabolism; D000890:Anti-Infective Agents / Q000494:pharmacology*; D005998:Glycine / Q000031:analogs & derivatives*; D006090:Gram-Negative Bacteria / Q000187:drug effects / Q000201:enzymology / Q000254:growth & development; D006094:Gram-Positive Bacteria / Q000187:drug effects / Q000201:enzymology / Q000254:growth & development; D006877:Hydroxamic Acids / Q000494:pharmacology*; D063208:Methionyl Aminopeptidases; D008826:Microbial Sensitivity Tests; D010797:Phthalimides / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D015003:Yeasts / Q000187:drug effects / Q000254:growth & development; D015091:beta-Alanine / Q000031:analogs & derivatives*
D000890:Anti-Infective Agents; D006877:Hydroxamic Acids; D010797:Phthalimides; D015091:beta-Alanine; D000626:Aminopeptidases; D063208:Methionyl Aminopeptidases; D000581:Amidohydrolases; C084507:peptide deformylase; D005998:Glycine