PROGRAM 4 - BASIC AND BORDER RESEARCH - PROJECTS FOR EXPLORATORY RESEARCH - PCE 2016
Cod: PN-III-P4-ID-PCE-2016-0519 Contract: 110/2017 Project director: CS I Dr. Marieta Nichifor Funding Agency: UEFISCDI Contractor: "Petru Poni" Institute of Macromolecular Chemistry, Iasi Project duration: 30 month Buget: 850.000 lei 2017: 291.596 lei 2018: 294.916 lei 2019: 263.488 lei Project description (Abstract): The main objective of the project is to design, synthesize and evaluate new more biocompatible materials of high complexity with enhanced antimicrobial activity against a wide number of gram positive and gram negative bacteria, yeasts and fungi, with application both as antibiotics alternatives and external powerful biocides. Selective antimicrobial polymers with a chemical structure mimimcking that of antimicrobial peptides, nameley the presence of a rigid facially amphiphilic main chain and amino groups of glycine or lysine type, will be prepared as antibiotic replacements.This goal will be achieved by using bile acids as starting materials. Bile acids are natural compounds with facial amphiphilicity and reactive groups (OH, COOH) which can be converted, by properly selected synthetic strategies, to derivatives able to give rise to bile acid oligomers carrying amino groups. Amphiphilic polymers with quaternary ammonium groups attached to polysaccharide (dextran, chitosan) backbone will be prepared as biocides. The hydrophobic part (alkyl, alkene chain, steroid), of these amphiphiles will be introduced as an end chain of the polysaccharide. The polymer characterisitics (nature of the bacbone and amino groups, amino group density, hydrophilic-lipophilic balance, molecular weight) determining the antimicrobial properties and occurrence of organized structures (micelles) will be preponderantly followed. Oligomer membrane activity will be tested on model lipid membrane with different compositions close to those of bacteria and red blood cells. Antimicrobial activity will be evaluated by minimal inhibitory and bactericidal concentration, and selectivity towards bacteria will be quantified by comparing the toxicity against bacteria and red blood cells. The new polymer architectures will aid to develop a theoretical background for the processes involved in interaction with bacteria and blood cells and for the influence of polymer structure on these processes. |