Khazna Alenezi1, Artak Tovmasyan2, Ines Batinic-Haberle2, Ludmil T Benov3. 1. Department of Medicine, Faculty of Medicine, Kuwait University, Kuwait. 2. Department of Radiation Oncology, Duke University Medical Center, USA. 3. Department of Biochemistry, Faculty of Medicine, Kuwait University, Kuwait. Electronic address: lbenov@hsc.edu.kw.
Abstract
INTRODUCTION: Efficient photodynamic inactivation of microbes requires highly efficient photosensitizers which kill microbial cells, but spare host tissues. One way to achieve such selectivity is to use photosensitizers that are rapidly taken up by microbes and, when applied at low concentrations, efficiently kill them after a short illumination. Design of such photosensitizers requires insight into molecular properties which are critical for antimicrobial photo-efficiency. This study explores the contribution of molecular shape and exposure of charges, to the antimicrobial activity of tetra-cationic Zn porphyrin-based photosensitizers. MATERIALS AND METHODS: Two isomers, ortho (2) and meta (3) hexyl and octyl Zn(II) meso-tetrakis(N-alkylpyridinium-2(3)-yl)porphyrins [ZnTnHex-2(3)-PyP and ZnTnOct-2(3)-PyP] were compared for uptake and photo-efficiency against a Gram-negative bacterium, Escherichia coli. RESULTS: The highest photo-efficiency was displayed by the meta hexyl derivative. At concentration as low as 1.0μM and during only 5min of preincubation with the cells, ZnTnHex-3-PyP decreased viable cell number by about 6log10 after only 5min of illumination. Since bacterial suspensions were thoroughly washed after preincubation with photosensitizers, this effect can be attributed only to photosensitizer taken up or bound to E. coli. Irrespective of its highest uptake by the cells, the octyl meta isomer, ZnTnOct-3-PyP, did not show higher antibacterial activity than the shorter-chain hexyl derivative, ZnTnHex-3-PyP. CONCLUSION: Efficiency and eventually selectivity of antimicrobial photosensitizers can be improved by optimizing the shape of the molecule and the position of electric charges. Increasing lipophilicity and cellular uptake per se, does not necessarily materialize in high antimicrobial efficiency of the photosensitizer.
INTRODUCTION: Efficient photodynamic inactivation of microbes requires highly efficient photosensitizers which kill microbial cells, but spare host tissues. One way to achieve such selectivity is to use photosensitizers that are rapidly taken up by microbes and, when applied at low concentrations, efficiently kill them after a short illumination. Design of such photosensitizers requires insight into molecular properties which are critical for antimicrobial photo-efficiency. This study explores the contribution of molecular shape and exposure of charges, to the antimicrobial activity of tetra-cationic Zn porphyrin-based photosensitizers. MATERIALS AND METHODS: Two isomers, ortho (2) and meta (3) hexyl and octyl Zn(II) meso-tetrakis(N-alkylpyridinium-2(3)-yl)porphyrins [ZnTnHex-2(3)-PyP and ZnTnOct-2(3)-PyP] were compared for uptake and photo-efficiency against a Gram-negative bacterium, Escherichia coli. RESULTS: The highest photo-efficiency was displayed by the meta hexyl derivative. At concentration as low as 1.0μM and during only 5min of preincubation with the cells, ZnTnHex-3-PyP decreased viable cell number by about 6log10 after only 5min of illumination. Since bacterial suspensions were thoroughly washed after preincubation with photosensitizers, this effect can be attributed only to photosensitizer taken up or bound to E. coli. Irrespective of its highest uptake by the cells, the octyl meta isomer, ZnTnOct-3-PyP, did not show higher antibacterial activity than the shorter-chain hexyl derivative, ZnTnHex-3-PyP. CONCLUSION: Efficiency and eventually selectivity of antimicrobial photosensitizers can be improved by optimizing the shape of the molecule and the position of electric charges. Increasing lipophilicity and cellular uptake per se, does not necessarily materialize in high antimicrobial efficiency of the photosensitizer.
Authors: Sueden O Souza; Bruno L Raposo; José F Sarmento-Neto; Júlio S Rebouças; Danielle P C Macêdo; Regina C B Q Figueiredo; Beate S Santos; Anderson Z Freitas; Paulo E Cabral Filho; Martha S Ribeiro; Adriana Fontes Journal: J Fungi (Basel) Date: 2022-05-25