Synthesis, physicochemical properties and membrane interaction of novel quaternary ammonium surfactants derived from L-Tyrosine and L-DOPA in relation to their antimicrobial, hemolytic activities and in vitro cytotoxicity

摘要

Novel quaternary ammonium compounds (QUATS) derived from L-Tyrosine and L-3,4-dihydroxyphenylalanine (L-DOPA) with chain lengths varying from C-10 to C-16 were synthesised and their physicochemical properties were determined. The CMCs of the QUATS were higher than their corresponding ester hydrochloride derivatives due to the increase in bulkiness of the head group in the micellar structure as confirmed by H-1 NMR spectroscopic investigations of the QUATS in DMSO d(6)-D2O system. The antibacterial effectiveness of the QUATS was evaluated against gram positive and gram negative bacteria and was found to possess good to excellent antibacterial properties. The QUAT tyrosine derivatives showed an optimum activity at C-14 and C-12 with respect to gram positive and negative strains respectively, while the C-12 QUAT DOPA derivative displayed optimal activity against both strains. The elucidation of their mode of action was studied by their interaction with 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) vesicles and the QUATS were found to interact with DPPC via both electrostatic and hydrophobic interactions. The toxicity of these compounds was assessed by their hemolytic activities and in vitro cytotoxicity against epidermoid carcinoma (KB) and lung fibroplast cells (MRC-5). Correlation of the MIC and HC50 with the CMC showed that the monomeric form of the QUATS displayed better antibacterial and lower hemolytic activities over their micellar form, showing that these compounds can act as antibacterial agents at monomeric concentrations, yet being non-hemolytic at these concentrations. Cytotoxicity evaluation showed an increase in activity with chain length of the tyrosine QUATS, with an increasing selectivity towards the cancer cells over normal cells. (C) 2016 Elsevier B.V. All rights reserved.