title: In vitro studies of antimicrobial activity of Gly-His-Lys conjugates as potential and promising candidates for therapeutics in skin and tissue infections.
abstract: In this Letter, we presented in vitro studies of antimicrobial activity of Gly-His-Lys conjugates that are important point in preliminary biological evaluation of their potential application in skin and tissue therapies. The novel compounds include the conjugation of fatty acids with a modification of the amino acid sequence in the primary structure of Gly-His-Lys (6i). All the compounds exhibited strong to moderate activity. Compound 1d had the most potent antimicrobial activity at MIC ranges 31.3-125.0μg/mL (against Escherichia coli spp. and Staphylococcus aureus spp.), 375.0-500.0μg/mL (against Pseudomonas aeruginosa spp.). Conjugate 5b expressed activity against Staphylococcus aureus spp. and Escherichia coli spp. at MIC ranges 250.0-500.0μg/mL and 62.5-125.0μg/mL, respectively. Both conjugates 1d and 5b possessed rapid bactericidal activity against Gram-positive bacteria at 2MIC or 4MIC. Conjugates 1b-c, 1e, 2a-b and 4b showed noticeable effect against both Gram-positive and Gram-negative bacteria. Compounds 1d, 1e and 2e were the most active against fungus.
authors.affiliation: Department of Organic Chemistry, Chemical Faculty, Gdansk University of Technology, 11/12 G. Narutowicza Street, 80-233 Gdansk, Poland. Electronic address: m-kukowska@wp.pl.
authors.forename: Monika
authors.initials: M
authors.lastname: Kukowska
authors.affiliation: Department of Organic Chemistry, Chemical Faculty, Gdansk University of Technology, 11/12 G. Narutowicza Street, 80-233 Gdansk, Poland.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Kukowska-Kaszuba
authors.affiliation: Department of Organic Chemistry, Chemical Faculty, Gdansk University of Technology, 11/12 G. Narutowicza Street, 80-233 Gdansk, Poland.
authors.forename: Krystyna
authors.initials: K
authors.lastname: Dzierzbicka
mesh_terms: D000890:Anti-Infective Agents / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D016470:Bacteremia / Q000188:drug therapy / Q000382:microbiology; D004926:Escherichia coli / Q000187:drug effects; D005658:Fungi / Q000187:drug effects; D006801:Humans; D008826:Microbial Sensitivity Tests; D009842:Oligopeptides / Q000737:chemistry*; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D017192:Skin Diseases, Bacterial / Q000188:drug therapy / Q000382:microbiology; D013211:Staphylococcus aureus / Q000187:drug effects
chemical_list: D000890:Anti-Infective Agents; D009842:Oligopeptides; C020905:glycyl-histidyl-lysine
keywords: Antimicrobial peptide; Fatty acid; Gly-His-Lys; Lipopeptide; Skin and tissue infections; Therapeutics