Antimicrobial and anticancer potential of novel polyaspartate derivatives synthesized via quaternary ammonium grafting

摘要

Three novel polyaspartate derivatives with antibacterial properties and low hemolytic effects are synthesized by the reaction of sodium polyaspartate (PAspNa) with different quaternary ammonium salts with a carboxylic end-group, subsequently these are tested in vitro against different cancer and normal cell lines. 1-(carboxypentyl) pyridinium bromide, 1-(carboxypentyl) benzalkonium bromide, and 1-(carboxypentyl) quinolinium bromide are synthesized from a quaternization reaction between 6-bromohexanoic acid and the respective tertiary amines (pyridine, N,N-dimethylbenzylamine, and quinoline). Then, these ammonium salts are chemically grafted along the sodium polyaspartate macromolecular chains through an acid-base reaction. Three different polyaspartate derivatives are obtained and their chemical structures analyzed and confirmed by FT-IR and H-1 NMR, the corresponding thermal stability is analyzed by thermogravimetric analysis. The antibacterial efficiency of these PAspNa derivatives against Escherichia coli is determined by measuring the minimum inhibitory concentration and the minimum bactericidal concentration. Hemolysis assays are performed on isolated human erythrocytes and finally the cell proliferation is studied by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) analysis. All the PAspNa derivatives show antibacterial activities, low hemolytic effects, and antiproliferative effect in some concentrations evaluated in murine fibroblast (3T3), and cancer cell lines of cervix (HeLa), breast (4T1), and liver (HepG2) cells lines.