Chitosan-hydroxycinnamic acid conjugates: Optimization of the synthesis and investigation of the structure activity relationship

• Main Authors: Nagy, Vivien, Sahariah, Priyanka, Hjálmarsdóttir, Martha Ásdís, Másson, Már
• Other Authors: Lyfjafræðideild (HÍ), Faculty of Pharmaceutical Sciences (UI), Heilbrigðisvísindasvið (HÍ), School of Health Sciences (UI), Háskóli Íslands, University of Iceland
• Format: Article in Journal/Newspaper
• Language: English
• Published: Elsevier 2022
• Subjects: Chitosan; Antioxidant; Antibacterial; Chemical modification; Protection groups; Design of Experiment (DOE); Kítósan; Andoxunarefni; Lyfjafræði; Iceland
• Online Access: https://hdl.handle.net/20.500.11815/3997; https://doi.org/10.1016/j.carbpol.2021.118896

A new synthesis method was developed and optimized by a full factorial design for conjugating hydroxycinnamic acids (HCA-s) to chitosan. Cinnamic acid and tert-butyldimethylsilyl protected HCA-s were converted to their corresponding acyl chlorides and reacted with 3,6-di-O-tert-butyldimethylsilyl-chitosan to selectively form amide linkages, resulting in water-soluble conjugates after deprotection. Nineteen conjugates were obtained with various degrees of substitution (DS) ranging from 3% to 60%. The conjugates were found to be bactericidal against Staphylococcus aureus and Escherichia coli, with their activities equal to chitosan at low DS but an increase in the DS correlated with reduced activity. DPPH (2,2-diphenyl-1-picrylhydrazyl) scavenging assay was performed to determine the EC50 values. Chitosan only exhibited low antioxidant activity, whereas the HCAchitosan conjugates exhibited higher antioxidant activities correlating with the DS. One caffeic acid conjugate (21%) was 4000 times more active than chitosan and more active than free caffeic acid. The research work was funded by the Icelandic Research Fund (Rannis Grant No. 185188-053) and by a doctoral grant from the University of Iceland research fund. Pre-print (óritrýnt handrit)