Antibacterial activity of N-quaternary chitosan derivatives: Synthesis, characterization and structure activity relationship (SAR) investigations |
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Authors: | Ö gmundur Vidar Rú narsson,Clemens Malainer,Há kon Steinsson,Tapio Nevalainen |
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Affiliation: | a Faculty of Pharmaceutical Sciences, School of Health Science, University of Iceland, Hofsvallagata 53, IS-107 Reykjavik, Iceland b Department of Pharmaceutical Chemistry, University of Kuopio, P.O. Box 1627, FIN-70211 Kuopio, Finland c University of Applied Science, FH Campus Wien, Biotechnologie Section, Campus Vienna BioCenter, Viehmarktgasse 2A/EG, 1030 Vienna, Austria d Faculty of Medicine, School of Health Science, University of Iceland, IS-107 Reykjavik, Iceland e Fennopharma Ltd, Mikrokatu 1, 70210 Kuopio, Finland |
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Abstract: | Quaternary N-(2-(N,N,N-tri-alkyl ammoniumyl and 2-pyridiniumyl) acetyl) derivatives of chitosan polymer, chitooligomer, and glucosamine (monomer) were synthesized for the purpose of investigating the structure activity relationship (SAR) for the antibacterial effect. Novel methods were used in the synthesis. The final chitosan and chitooligomer derivatives could thus be obtained in two steps without prior protection of the hydroxyl groups. However, in order to obtain chitosan derivatives with the bulky N,N-dimethyl-N-dodecyl- and N,N-dimethyl-N-butyl side chains three steps were needed, starting from 3,6-O-di-tert-butyldimethylsilyl chitosan (3,6-O-di-TBDMS chitosan) as the key intermediate. The quaternary ammoniumyl acetyl derivatives of glucosamine were synthesized from glucosamine or tetra-O-acetylglucosamine. N,N,N-trimethyl chitosan (TMC) was used as reference compound for investigation of antibacterial activity. Clinical Laboratory Standard Institute (CLSI) protocols were used to determine MIC and MLC for activity against clinically important Gram-positive strains Staphylococcus aureus (ATCC 25923), and S. aureus (MRSA) (ATCC 43300), and Gram-negative strains of Escherichia coli (ATCC 25922), P. aeriginosa (ATCC 27853) and Enterococcus facialis (ATCC 29212). The MIC values for the compounds ranged from 8 to ?8192 mg/L. In general the N-(2-(N,N-dimethyl-N-dodecyl ammoniumyl) acetyl) derivatives of chitooligomer and glucosamine monomer were more active against bacteria than derivatives with shorter alkyl chains. In contrast the N-(2-(N,N-dimethyl-N-dodecyl ammoniumyl) acetyl) derivatives of chitosan were less active than derivatives with N-(2-N,N,N-trimetylammoniumyl) acetyl or N-(2-(N-pyridiniumyl) acetyl) quaternary moiety. N,N,N-trimethyl chitosan (TMC) was the most active compound in this study. |
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Keywords: | Chitosan Trimethyl chitosan tert-Butyldimethylsilyl chitosan Quaternary ammonium Antibacterial activity SAR |
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