Selective synthesis of N,N,N-trimethylated chitosan derivatives at different degree of substitution and investigation of structure-activity relationship for activity against P. aeruginosa and MRSA
| Autor: | Sigríður Ólafsdóttir, Sigríður Jónsdóttir, Sankar Rathinam, Már Másson, Martha Á. Hjálmarsdóttir |
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| Rok vydání: | 2020 |
| Předmět: |
Methicillin-Resistant Staphylococcus aureus
Stereochemistry Microbial Sensitivity Tests 02 engineering and technology Biochemistry Chitosan Structure-Activity Relationship 03 medical and health sciences chemistry.chemical_compound Degree of substitution Structural Biology Cations Structure–activity relationship Molecular Biology 030304 developmental biology 0303 health sciences Broth microdilution Cationic polymerization General Medicine 021001 nanoscience & nanotechnology Antimicrobial Anti-Bacterial Agents chemistry Pseudomonas aeruginosa 0210 nano-technology |
| Zdroj: | International Journal of Biological Macromolecules. 160:548-557 |
| ISSN: | 0141-8130 |
| DOI: | 10.1016/j.ijbiomac.2020.05.109 |
| Popis: | Two new cationic chitosan derivatives were synthesized using a combination of Boc and TBDMS protection strategies. This included a series of six samples of the TMCNH2/TM derivative, where some of the amino groups were N,N,N-trimethylated and the remaining was in the primary state. A series of six samples of the TACin derivative, where some of the amino groups were N-acetylated with quaternary 2-(N,N,N-trimethylammoniumyl) acetyl group and the remaining fully N-acetylated, were also synthesized. The degree of substitution (DS) for quaternary amino groups in these series ranged from 0.06–0.89. TMCDM/TM derivatives with a mix of N,N,N-trimethylated and N,N-dimethylated groups were also synthesized according to a published procedure but in this case, it was more difficult to control the DS than with the TBDMS protection strategy. Broth microdilution assay revealed a markedly different structure-activity relationship (SAR) for the two derivatives. The activity for the TMC derivatives reached a plateau above 0.2–0.3 DS whereas the activity increased continuously with DS for TACin. The highest DS TMCNH2/TM was more active than the highest DS, TACin, against Gram-positive MRSA but less active against the Gram-negative P. aeruginosa. |
| Databáze: | OpenAIRE |
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