Institute of Physical Chemistry, Polish Academy of Sciences, 01-224, Warsaw, Kasprzaka 44/52, Poland.
Institute of Physical Chemistry, Polish Academy of Sciences, 01-224, Warsaw, Kasprzaka 44/52, Poland.
Eur J Med Chem. 2020 Aug 15;200:112472. doi: 10.1016/j.ejmech.2020.112472. Epub 2020 May 18.
Considering the world-wide problem of growing antibiotic resistance of bacteria, photodynamic inactivation (PDI) has a potential to become the treatment approach against some infectious diseases. In our study, four differently substituted porphycenes were compared in terms of their bactericidal activity against E. faecalis. All tested compounds had a similar photophysical characteristics, i.e., there were no significant differences in the location of absorption bands or molar absorption coefficients. Also, singlet oxygen generation quantum yields were very similar. Surprisingly, differently substituted porphycenes caused very diverse PDI effects. Special attention was drawn to the tert-butyl moieties. Our studies demonstrated that the presence of these substituents lowers the bactericidal potential significantly and can completely block the activity when more than one moiety is introduced to the molecule. The porphycenes lacking tert-butyl groups exhibited much higher PDI potential and we assign this effect to different interactions of the differently substituted porphycenes with the bacterial cells. Most likely, the presence of tert-butyls impairs cell penetration by the photosensitizer. These results remind that the favorable photophysical characteristics do not ensure that the compound considered as a potential PDI agent can reach the microbial cells.
鉴于全球范围内细菌对抗生素耐药性的问题日益严重，光动力灭活（PDI）有可能成为治疗某些传染病的方法。在我们的研究中，比较了四种不同取代的卟啉，以评估它们对粪肠球菌的杀菌活性。所有测试的化合物都具有相似的光物理特性，即吸收带的位置或摩尔吸光系数没有明显差异。同样，单线态氧生成量子产率也非常相似。令人惊讶的是，不同取代的卟啉导致了非常不同的 PDI 效应。特别注意到叔丁基部分。我们的研究表明，这些取代基的存在会显著降低杀菌潜力，并且当分子中引入一个以上的取代基时，可完全阻断其活性。缺乏叔丁基的卟啉表现出更高的 PDI 潜力，我们将这种效应归因于不同取代的卟啉与细菌细胞的不同相互作用。很可能，叔丁基的存在会阻碍光敏剂穿透细胞。这些结果提醒人们，有利的光物理特性并不能保证被认为是潜在 PDI 剂的化合物能够到达微生物细胞。
