Chitosan derivatives targeting lipid bilayers: Synthesis, biological activity and interaction with model membranes

Author(s)

Martins, Danubia Batista ; Nasario, Fabio Domingues ^[1] ; Silva-Goncalves, Laiz Costa ^[2] ; de Oliveira Tiera, Vera Aparecida ^[1] ; Arcisio-Miranda, Manoel ^[2] ; Tiera, Marcio Jose ^[1] ; dos Santos Cabrera, Marcia Perez ^{[1, 3]}

Affiliation

^[1] Univ Estadual Paulista Unesp, Dept Quim & Ciencias Ambientais, Inst Biociencias Letras & Ciencias Exatas Ibilce, Campus Sao Jose do Rio Preto, BR-15054000 Sao Jose Do Rio Preto, SP - Brazil

^[2] Univ Fed Sao Paulo, Lab Neurobiol Estrutural & Func LaNEF, Dept Biofis, R Botucatu 862, BR-04023062 Sao Paulo, SP - Brazil

^[3] Univ Estadual Paulista Unesp, Dept Fis, Inst Biociencias Letras & Ciencias Exatas Ibilce, Campus Sao Jose do Rio Preto, BR-15054000 Sao Jose Do Rio Preto, SP - Brazil

• Document type: Journal article
• Source: Carbohydrate Polymers; v. 181, p. 1213-1223, FEB 1 2018.
• Web of Science Citations: 6

Abstract

The antimicrobial activity of chitosan and derivatives to human and plant pathogens represents a high-valued prospective market. Presently, two low molecular weight derivatives, endowed with hydrophobic and cationic character at different ratios were synthesized and characterized. They exhibit antimicrobial activity and increased performance in relation to the intermediate and starting compounds. However, just the derivative with higher cationic character showed cytotoxicity towards human cervical carcinoma cells. Considering cell membranes as targets, the mode of action was investigated through the interaction with model lipid vesicles mimicking bacterial, tumoral and erythrocyte membranes. Intense lytic activity and binding are demonstrated for both derivatives in anionic bilayers. The less charged compound exhibits slightly improved selectivity towards bacterial model membranes, suggesting that balancing its hydrophobic/hydrophilic character may improve efficiency. Observing the aggregation of vesicles, we hypothesize that the ``charge cluster mechanism{''}, ascribed to some antimicrobial peptides, could be applied to these chitosan derivatives. (AU)

• FAPESP's process: 12/02065-0 - Electrophysiology of antimicrobial peptides in planar lipid bilayers
• Grantee: Manoel de Arcisio Miranda Filho
• Support Opportunities: Regular Research Grants
• FAPESP's process: 09/11707-2 - Synthesis and Characterization of Cationic Derivatives of Chitosan and their interaction with Vesicles of DPPC.
• Grantee: Fábio Domingues Nasário
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• FAPESP's process: 10/11823-0 - Mechanisms of interactions of lipid bilayers and amphiphilic substances of therapeutic interest
• Grantee: Marcia Perez dos Santos Cabrera
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 12/24259-0 - Peptide and chitosan conjugates with pharmacological potential: synthesis, prospecting of activity in membrane mimetic systems, and evaluation in cells
• Grantee: Marcia Perez dos Santos Cabrera
• Support Opportunities: Research Grants - Young Investigators Grants
• FAPESP's process: 12/03619-9 - Biofungicides: synteses and characterization anphiphilic derivatives of chitosan for application against Aspergillus genus species
• Grantee: Vera Aparecida de Oliveira Tiera
• Support Opportunities: Regular Research Grants
• FAPESP's process: 14/08372-7 - Peptide and chitosan conjugates with pharmacological potential: synthesis, prospecting of activity in membrane mimetic systems, and evaluation in cells
• Grantee: Marcia Perez dos Santos Cabrera
• Support Opportunities: Scholarships in Brazil - Young Researchers