Department of Chemistry, QOPNA, University of Aveiro, Campus of Santiago, Aveiro, Portugal.
Photochem Photobiol Sci. 2012 Dec;11(12):1905-13. doi: 10.1039/c2pp25113b.
Photodynamic inactivation (PDI) is an efficient approach against a wide range of microorganisms and can be viewed as an alternative for the treatment of microbial infections. In this work we synthesized "first" and "second" generation photosensitizers (PSs), the tetra-cationic porphyrin and the new penta-cationic chlorin , respectively, and evaluated their efficiency against two antibiotic resistant bacterial strains, Staphylococcus aureus and Pseudomonas aeruginosa. The PS was obtained in very good yield by an easy synthesis method. The PDI studies were performed in parallel with 5,10,15,20-tetrakis(1-methylpyridinium-4-yl)porphyrin tetra-iodide (), a widely studied PS in PDI, and the obtained results were compared. Two different light ranges were used: white light (400-800 nm) and red light (530-800 nm) delivered at a fluence rate of 150 mW cm(-2). The results show that both strains, even though antibiotic resistant, were efficiently inactivated by the three PSs, chlorin being the most effective. For the Gram positive bacterium S. aureus a 7.0 log reduction was observed after 5-10 min of irradiation, at a concentration of 0.5 μM, whereas for the Gram negative P. aeruginosa, similar photoinactivation occurred at a higher PS concentration (10 μM) and after a longer irradiation period (30 min). The synthetic chlorin can be regarded as promising for the treatment of bacterial infections under red light, which penetrates deeper in living tissues. The results of this study open the possibility to prepare a new series of chlorin-type derivatives to efficiently photoinactivate Gram (+) and (-) antibiotic resistant bacteria. The efficient PDI with the chlorin indicates high potential for the use of a scaffold in the preparation of new generation PSs based on cationic chlorin derivatives.
光动力灭活（PDI）是一种有效对抗多种微生物的方法，可以作为治疗微生物感染的替代方法。在这项工作中，我们分别合成了“第一代”和“第二代”光敏剂（PS），即四阳离子卟啉和新的五阳离子氯卟啉，并评估了它们对两种抗生素耐药细菌金黄色葡萄球菌和铜绿假单胞菌的效率。PS 通过一种简单的合成方法以很好的产率获得。PDI 研究与广泛用于 PDI 的 5,10,15,20-四（1-甲基吡啶-4-基）卟啉四碘化物（）同时进行，并比较了获得的结果。使用了两种不同的光照范围：白光（400-800nm）和红光（530-800nm），辐照度为 150mWcm(-2)。结果表明，即使是抗生素耐药的两种菌株，也都被三种 PSs 有效地灭活，氯卟啉的效果最显著。对于革兰氏阳性菌金黄色葡萄球菌，在 0.5μM 的浓度下，照射 5-10 分钟后观察到 7.0 个对数减少，而对于革兰氏阴性菌铜绿假单胞菌，在更高的 PS 浓度（10μM）和更长的照射时间（30 分钟）后，也发生了类似的光灭活。合成的氯卟啉可被视为在红光下治疗细菌感染的有前途的候选药物，因为红光在活组织中穿透更深。这项研究的结果为制备新型氯卟啉衍生物以有效光灭活革兰氏（+）和（-）抗生素耐药细菌开辟了可能性。氯卟啉的高效 PDI 表明，基于阳离子氯卟啉衍生物的新一代 PS 的制备中使用支架具有很高的潜力。
