Synthesis and investigation of novel chlorin sensitizers containing the myristic acid residue for antimicrobial photodynamic therapy

Abstract

This paper describes the results of our extensive and continuing series of studies on the development and investigation of new potential sensitizers for antitumor and antimicrobial photodynamic therapy (APDT) based on a macroheterocyclic platform. Here we focus on synthesis, identification, phase distribution and antimicrobial activity of two novel chlorin-type photosensitizers (PSs) containing the fragment of myristic acid to enhance their membrane permeability and toxicity towards microbial cells. Pheophorbide a 17(3)-methyl ester has been functionalized by the covalent attachment of the myristic acid residue. To increase solubility in aqueous media and affinity to the outer membrane of Gram-negative bacteria, two charged –N(CH3)3+ groups have been additionally attached. Both neutral and cationic pigments have been identified via UV-Vis, emission, IR-, NMR- and MS-spectra. The cationic PS has been additionally identified with the HQLC technique. PSs were found to be soluble and stable in diluted aqueous solutions of non-ionic surfactant Tween 80 and revealed pronounced affinity to a lipid-like environment. The investigation of their antimicrobial activity in vitro has indicated that PSs are able to kill both archival opportunistic microorganisms and Gram-negative hospital-acquired bacteria. The cationic chlorin has also demonstrated efficient photoinactivation of antibiotic resistant strains of Pseudomonas aeroginosa and Escherichia coli in the animal model of a wound infection. The results obtained reveal its great potential for treating many drug-resistant infections induced both bacteria and fungi.