title: Synthesis of guanidinylated chitosan with the aid of multiple protecting groups and investigation of antibacterial activity.
abstract: A new synthetic approach employing two types of protecting groups, tertiarybutyldimethylsilyl (TBDMS) and tertiarybutyloxycarbonyl (Boc) was developed to obtain a series of guanidinylated chitosan derivatives. The synthesis was carried out in organic solvents which allowed quantitative reaction, a good control on the degree of substitution, and 100% substitution of the chitosan amino groups. Similar derivatives carrying the trimethylammonium group were also synthesized as reference compounds. All the derivatives were characterized using (1)H and COSY NMR and IR spectroscopy. The antibacterial effect against clinically relevant strains of S. aureus and E. coli was found to increase with increase in the degree of substitution and decrease in the spacer length of the derivatives in both the series. An optimum activity could be obtained at a degree of substitution above 0.5 for most derivatives. The trimethylammonium derivatives showed slightly higher activity than the corresponding guanidinium derivatives but a similar structure-activity relationship was obtained.
authors.affiliation: Faculty of Pharmaceutical Sciences, School of Health Sciences, University of Iceland, Hofsvallagata 53, IS-107 Reykjavík, Iceland.
authors.forename: Priyanka
authors.initials: P
authors.lastname: Sahariah
authors.affiliation: Faculty of Pharmaceutical Sciences, School of Health Sciences, University of Iceland, Hofsvallagata 53, IS-107 Reykjavík, Iceland.
authors.forename: Bjarni M
authors.initials: BM
authors.lastname: Óskarsson
authors.affiliation: Department of Biomedical Science, Faculty of Medicine, University of Iceland, Stapi, Hringbraut 31, 101 Reykjavík, Iceland.
authors.forename: Martha Á
authors.initials: MÁ
authors.lastname: Hjálmarsdóttir
authors.affiliation: Faculty of Pharmaceutical Sciences, School of Health Sciences, University of Iceland, Hofsvallagata 53, IS-107 Reykjavík, Iceland. Electronic address: mmasson@hi.is.
authors.forename: Már
authors.initials: M
authors.lastname: Másson
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D048271:Chitosan / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004926:Escherichia coli / Q000187:drug effects*; D019791:Guanidine / Q000737:chemistry*; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D008970:Molecular Weight; D013211:Staphylococcus aureus / Q000187:drug effects*; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D048271:Chitosan; D019791:Guanidine
keywords: Antibacterial activity; Guanidinyl chitosan; Quaternary ammoniumyl chitosan; Silyl chitosan; Structure–activity relationship (SAR); Trimethyl chitosan (TMC)