Antimicrobial activity of N-phthaloylamino acid hydroxamates

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.
Ispitano je djelovanje N-ftaloil-aminokiselinskih hidroksamata 1–3 opće formule C6H4(CO)2N-X-CONHOH (X = aminokiselinski ostatak glicina, -alanina ili D-fenilglicina) na 44 soja Gram-pozitivnih i Gram-negativnih bakterija i 10 vrsta kvasaca. Antibakterijski i antifungalni učinak testiran je postupkom difuzije na hranjivom agaru i standardnom metodom dilucije. Najbolja inhibicija rasta, osobito izražena prema Gram-negativnim bakterijama, utvrđena je za N-ftaloil-D-fenilglicin hidroksamsku kiselinu (3) s najvećom lipofilnošću. Za soj Yersinia enterocolitica O3 minimalna inhibitorna koncentracija (0,008 mg mL–1) potvrđena je inhibicijskom zonom od 30 mm pomoću difuzijskog testa. Hidroksamati inhibiraju rast keliranjem metala PDF enzima kod Gram-pozitivnih i Gram-negativnih bakterija, te LpxC enzima kod Gram-negativnih bakterija. Ftalimido struktura pridonosi inhibiciji, pretpostavlja se, destabilizacijom m-RNA. Antifungalna aktivnost spojeva 1–3 nije osobito izražena.