ABSTRACT
Heat, acid and base stress methods were applied to study the stability of squalamine lactate. Liquid chromatography coupled with mass spectrometry was used to analyze the degraded samples and tentative structural identifications were assigned based on their molecular weight measurements, reactivity and MS/MS fragmentation. Solid squalamine lactate generated a new amide, namely lactyl squalamide, when heated to 80 degrees C. Chemical structure for this new compound has been established by NMR and MS data interpretation and confirmed by direct comparison between the degradant and the synthesized compound. Squalamine lactate in pH 4 acetate buffer solution produced more degradants under stressed conditions. These degradants are formed due to the loss of the sulfate functionality. Squalamine lactate is stable in refrigerated conditions as well as in basic solution.
Subject(s)
Cholestanols/chemistry , Cholestanols/analysis , Chromatography, Liquid/methods , Drug Stability , Indicators and Reagents , Injections , Mass Spectrometry/methods , Reproducibility of Results , Sensitivity and SpecificityABSTRACT
Magainins are a family of potent antimicrobial cationic peptides that possess antimicrobial activity against a wide range of target organisms. In this study, the antimicrobial activity of synthetic magainin-mimetic compounds MSI-751 and MSI-774 was investigated against the periodontal pathogens Porphyromonas gingivalis, Fusobacterium nucleatum, Actinobacillus actinomycetemcomitans, Eikenella corrodens, Prevotella loescheii and Prevotella intermedia. P. gingivalis was more susceptible to MSI-751 than to MSI-774, whereas the other oral pathogens showed little difference in susceptibility to the two compounds. MSI-751 exhibited a rapid, dose-dependent bactericidal effect on P. gingivalis. Electron microscopy of MSI-751-treated P. gingivalis revealed intact cell wall vesicles devoid of cell contents, suggesting perturbation of the cytoplasmic membrane by this compound, perhaps equivalent to formation of membrane-disruptive ion channels by magainin peptides. These studies demonstrate that synthetic magainin derivatives exhibit antimicrobial activity against oral pathogens by disruption of cell membrane integrity.
