Experimental design for determining quantitative structure activity relationship for antibacterial chitosan derivatives

• Published in: Journal of Materials Chemistry B
• Main Authors: Sahariah, Priyanka, Snorradóttir, Bergthóra S., Hjálmarsdóttir, Martha Á., Sigurjónsson, Ólafur E., Másson, Már
• Other Authors: 1 Univ Iceland, Fac Pharmaceut Sci, Sch Hlth Sci, Hofsvallagata 53, IS-107 Reykjavik, Iceland 2 Univ Iceland, Fac Med, Dept Biomed Sci, Hringbraut 31, IS-101 Reykjavik, Iceland 3 Landspitali Univ Hosp, Blood Bank, REModeL Lab, Snorrabraut 60, IS-105 Reykjavik, Iceland Organization-Enhanced Name(s) Landspitali National University Hospital 4 Reykjavik Univ, Inst Biomed & Neural Engn, Menntavegur 1, IS-101 Reykjavik, Iceland
• Format: Article in Journal/Newspaper
• Language: English
• Published: Royal Soc Chemistry 2016
• Subjects: NAF12; BAB12; Anti-Infective Agents; Quartz Crystal Microbalance Techniques; Quaternary Ammonium Compounds; Retinoblastoma-Binding Protein 4; Nanoparticles; Biocompatible Materials; Methods; Chitin; Simeprevir; Iceland
• Online Access: http://hdl.handle.net/2336/618501; https://doi.org/10.1039/C6TB00546B

To access publisher's full text version of this article click on the hyperlink at the bottom of the page Experimental design approach was successfully used to guide the synthesis and determine the structure-activity relationship for antimicrobial derivatives of the biopolymer chitosan. Specialized software with D-optimal design capabilities was used to create a library of chitosan derivatives with optimal structural variation in order to conduct a detailed investigation of the structure-activity relationship. The derivatives contain three substituents: N,N,N-trimethylamine, N-acetyl and N-stearoyl at different degrees of substitution (DS) on the 2-amino group of chitosan. The design matrix consisted of 14 target materials that were synthesized in 'one-pot synthesis' using TBDMS-chitosan as the precursor to allow precise control of the DS. The antibacterial activity (MIC) towards the Gram positive bacteria Staphylococcus aureus and the Gram negative bacteria Escherichia coli, hemolytic activity (HC50) towards human red blood cells and solubility of the chitosan derivatives were used as the responses in the model. The response surface model was refined by removing the interaction terms to improve the statistical significance and predictive power of the model. The investigation showed that materials with DS for trimethylation in the range 0.45-0.65, acetylation in the range 0.08-0.33 and stearoylation in the range 0.22-0.29 were capable of showing high antimicrobial activity, high solubility and low hemolytic activity. Icelandic Research Fund/120443021 University of Iceland Research Fund Bergporu og Porsteins Schevings Thorsteinsson