title: Synthesis, micellisation and interaction of novel quaternary ammonium compounds derived from l-Phenylalanine with 1,2-dipalmitoyl-sn-glycero-3-phosphocholine as model membrane in relation to their antibacterial activity, and their selectivity over human red blood cells.
abstract: A series of quaternary ammonium compounds (QUATS) derived from l-Phenylalanine have been synthesized and their antibacterial efficiencies were determined against various strains of Gram-positive and Gram-negative bacteria. The antibacterial activity increased with increasing chain length, exhibiting a cut-off effect at C14 for Gram-positive and C12 for Gram-negative bacteria. The l-Phenylalanine QUATS displayed enhanced antibacterial properties with a higher cut-off point compared to their corresponding l-Phenylalanine ester hydrochlorides. The CMC was correlated with the MIC, inferring that micellar activity contributes to the cut-off effect in antibacterial activity. The hemolytic activities (HC50) of the QUATS against human red blood cells were also determined to illustrate the selectivity of these QUATS for bacterial over mammalian cells. In general, the MIC was lower than the HC50, and assessment of the micellar contribution to the antibacterial and hemolytic evaluation in TBS as a common medium confirmed that these QUATS can act as antibacterial, yet non-toxic molecules at their monomer concentrations. The interaction of the QUATS with the phospholipid vesicles (1,2-dipalmitoyl-sn-glycero-3-phosphocholine, DPPC) in the presence of 1-anilino-8-naphthalene sulfonate (ANS) and 1,6-diphenyl-1,3,5-hexatriene (DPH) as fluorescence probes showed that the presence of the quaternary ammonium moiety causes an increase in hydrophobic interactions, thus causing an increase in antibacterial activity.
authors.affiliation: Department of Chemistry, Faculty of Science, University of Mauritius, Réduit, Mauritius.
authors.forename: Nausheen
authors.initials: N
authors.lastname: Joondan
authors.affiliation: Department of Chemistry, Faculty of Science, University of Mauritius, Réduit, Mauritius.
authors.forename: Prakashanand
authors.initials: P
authors.lastname: Caumul
authors.affiliation: University of KwaZulu-Natal, Private Bag X01, Scottsville, Pietermaritzburg 3209, South Africa.
authors.forename: Matthew
authors.initials: M
authors.lastname: Akerman
authors.affiliation: Department of Chemistry, Faculty of Science, University of Mauritius, Réduit, Mauritius. Electronic address: sabina@uom.ac.mu.
authors.forename: Sabina
authors.initials: S
authors.lastname: Jhaumeer-Laulloo
mesh_terms: D015060:1,2-Dipalmitoylphosphatidylcholine / Q000031:analogs & derivatives* / Q000737:chemistry; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D066241:Carbon-13 Magnetic Resonance Spectroscopy; D018360:Crystallography, X-Ray; D004912:Erythrocytes / Q000187:drug effects*; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D008823:Micelles; D008956:Models, Chemical; D008958:Models, Molecular; D010649:Phenylalanine / Q000737:chemistry*; D066244:Proton Magnetic Resonance Spectroscopy; D000644:Quaternary Ammonium Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D008823:Micelles; D000644:Quaternary Ammonium Compounds; D015060:1,2-Dipalmitoylphosphatidylcholine; C081581:colfosceril palmitate; D010649:Phenylalanine
keywords: Antibacterial activity; Critical micelle concentration; Hemolytic activity; Phospholipid; l-Phenylalanine QUATS