Abstract
Light-mediated killing of pathogens by cationic photosensitizers (PS) is a promising antimicrobial approach avoiding resistance as being present upon the use of antibiotics. In this study we focused on the impact of the substituents in phenalen-1-one PS. Photodynamic efficacy depending on positively charged moieties including a primary aliphatic, quaternary aliphatic, aromatic ammonium and a guanidinium cation was investigated against Gram-positive and Gram-negative pathogens. Considering the altered steric demand and lipophilicity of these functional groups we deduced a structure-activity relationship. SAGUA was the most potent PS in this series reaching a maximum efficacy of ≥6log10 steps of bacteria killing at a concentration of 10 μM upon irradiation with blue light (20 mW cm(-2)) for 60 s (1.2 J cm(-2)) without exhibiting inherent dark toxicity. Its guanidinium moiety may be able to form strong bidentate and directional hydrogen bonds to carboxylate groups of bacterial surfaces in addition to ionic charge attraction. This may supplement fast and effective antimicrobial activity.
Highlights
The discovery of antibiotics can be seen as one of the most important breakthroughs in medical history
We evaluate a set of derivatives (Fig. 1) based on a phenalen-1-one structure (6), whereby the effect of the nature of the cationic substituents in the phenalen-1-one derivatives on the antimicrobial photodynamic efficacy is studied
The aim of this study is (i) to evaluate this new set of compounds based on a phenalen-1-one structure regarding their antimicrobial photodynamic efficacy, (ii) to deduce a structure–activity relationship concerning the effect of the nature of their cationic substituents on the antimicrobial efficacy and (iii) to study the efficacy under low light dose conditions using an optimized illumination device
Summary
The discovery of antibiotics can be seen as one of the most important breakthroughs in medical history. Antibiotics have revolutionized the way patients with bacterial infections are treated and have contributed to the reduction of the mortality and morbidity from bacterial diseases. Unconsidered and abundant use in human as well as in veterinary medicine and animal fattening contributed to the emergence of antibiotic-resistant strains, e.g. methicillin-resistant Staphylococcus aureus (MRSA) or vancomycin-resistant Enterococci (VRE) strains.[1] resistance against antiseptic and antimicrobial agents, which are clinically used, e.g. chlorhexidine[2] and triclosan,[3] is arising. The demand for developing alternative approaches for successful inactivation of pathogens is becoming more and more crucial. These alternative approaches should operate – different from antibiotics – not towards one specific target according to the so-called key-hole-principle, but as multi-target processes, in order to avoid development of resistance in microorganisms.[4,5]
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