Abstract：
Bacterial infections are a global health concern, particularly due to the increasing resistance of bacteria to antibiotics. Multi-drug resistance (MDR) is a considerable challenge, and novel approaches are needed to treat bacterial infections. Photodynamic inactivation (PDI) of microorganisms is increasingly recognized as an effective method to inactivate a broad spectrum of bacteria and overcome resistance mechanisms. This study presents the synthesis of a new cationic 5,15-di-imidazolyl porphyrin derivative and the impact of n-octanol/water partition coefficient (logP) values of this class of photosensitizers on PDI efficacy of Escherichia coli. The derivative with logP = -0.5, IP-H-OH2+, achieved a remarkable 3 log CFU reduction of E. coli at 100 nM with only 1.36 J/cm2 light dose at 415 nm, twice as effective as the second-best porphyrin IP-H-Me2+, of logP = -1.35. We relate the rapid uptake of IP-H-OH2+ by E. coli to improved PDI and the very low uptake of a fluorinated derivative, IP-H-CF32+, logP ≈ 1, to its poor performance. Combination of PDI with cinnamaldehyde, a major component of the cinnamon plant known to alter bacteria cell membranes, offered synergic inactivation of E. coli (7 log CFU reduction), using 50 nM of IP-H-OH2+ and just 1.36 J/cm2 light dose. The success of combining PDI with this natural compound broadens the scope of therapies for MDR infections that do not add drug resistance. In vivo studies on a mouse model of wound infection showed the potential of cationic 5,15-di-imidazolyl porphyrins to treat clinically relevant infected wounds.
摘要：
细菌感染是全球健康问题，特别是由于细菌对抗生素的耐药性增加。多重耐药性(MDR)是一个相当大的挑战,并且需要新的方法来治疗细菌感染。微生物的光动力灭活(PDI)越来越被认为是灭活广谱细菌和克服抗性机制的有效方法。这项研究介绍了一种新的阳离子5,15-二咪唑基卟啉衍生物的合成以及该类光敏剂的正辛醇/水分配系数（logP）值对大肠杆菌PDI功效的影响。logP=-0.5的导数，IP-H-OH2+，在415nm的光剂量仅为1.36J/cm2的情况下，在100nM时，大肠杆菌的CFU显著减少了3log，效果是第二好的卟啉IP-H-Me2+的两倍，logP=-1.35。我们将大肠杆菌对IP-H-OH2的快速摄取与改善的PDI和氟化衍生物的极低摄取联系起来，IP-H-CF32+,logP≈1，表现不佳。PDI与肉桂醛的组合，肉桂植物的主要成分，已知会改变细菌细胞膜，提供了大肠杆菌的协同灭活作用（7logCFU减少），使用50nM的IP-H-OH2+和仅1.36J/cm2的光剂量。PDI与这种天然化合物结合的成功扩大了MDR感染的治疗范围，而不会增加耐药性。对伤口感染小鼠模型的体内研究表明阳离子5,15-二-咪唑基卟啉治疗临床相关感染伤口的潜力。
