engleski

ANTIMICROBIAL ACTIVITY OF N-PHTHALOYL-GLYCINE- AND D-PHENYLGLYCINE-HYDROXAMIC ACIDS

Introduction: The investigated compounds N-phthaloyl-glycine- and N-phthaloyl- D-phenylglycine-hydroxamic acids exert in their structures two biological very active groups: N-hydroxyamide and phthalimido. Hydroxamic acid (HA), e.g. hydroxyurea and its derivatives are well known cytostatics. HA as inhibitors of some metalloproteinases involve chelation of metals. The most important is their ability to form chelates with Fe3+ ion. The well known phthalimide, thalidomide (α -phthalimidoglutarimide) is teratogenic. Pthalimidoalkanehydroxamic acids have a significant mitodepressive activity on Cresse seeds (Lepidium sativum L.) In the present study antimicrobial activity of two N-phthaloyl-aminoacid-hydroxamic acids are investigated. Materials and methods: N-phthaloyglycine- and N-phthaloyl- D-phenylglycine-hydroxamic acids were synthesized in the reaction of N-phthaloyl-aminoacid chlorides with hydroxylamine. The assay for inhibition of bacterial and yeasts were carried out by diffusion test on solid agar plates and broth dilution susceptibility test. The water dilutions of N-phthaloyl-glycine- and D-phenylglycine-hydroxamic acid were added to sterile steel cylinder (8x10mm) which were placed on agar previously inoculated with test microorganisms. A clear zone or ring is present around cylinder after incubation if the agent inhibits microbial growth. Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were established by dilution test. Results: The antibacterial activities of two cyclic HA were detected in 26 out of 30 tested strs. of various gram(+) and grand(-) bacteria. N-phthaloyl-glycine- hydroxamic acid was more effective as growth inhibitor on gram(+) bacteria. Agar diffusion test showed zone inhibition diameter of 12-20mm and concn. of 1, 33 mg/mL was bactericidal for all 16 susceptibility strains. Antibacterial activity of N-phthaloyl- D-phenylglycine-hydroxamic acid was observed in 26 strains with zone inhibition diameter of 13-32mm. Bactericidal concns. were between 0, 04-1, 33mg/mL. It was also observed that these two hydroxamic acids were inactive against 10 species of yeasts. Conclusion: This study demonstrates that both cyclic HA are effective antibacterial agents, but no antifungal agents. These activities appeared to be dependent on the hydroxamic acid function and were probably due to the interaction with DNA. D-phenylglycine-hydroxamic acid was distinctly more effective than N-phthaloyl-glycine acid which is seen from zone inhibition diameters and minimum bactericidal concentrations.

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