Department of Organic Chemistry, University of Regensburg, Regensburg, Germany.
Laboratory of Photodynamic Inactivation of Microorganisms, Department Cell Biology and Physiology, University of Salzburg, Salzburg, Austria.
Eur J Med Chem. 2018 Nov 5;159:423-440. doi: 10.1016/j.ejmech.2017.09.072. Epub 2017 Oct 21.
The naturally occurring photosensitizer curcumin has excellent biocompatibility, but its antimicrobial photodynamic efficacy is limited by (i) weak adherence to Gram(-) bacteria cell walls, (ii) low (photo-)stability and (iii) limited solubility in water. In this study novel curcuminoids bearing cationic substituents were prepared by different synthetic routes. The derivatives exhibit excellent water solubility, improved photostability and low aggregation. All novel curcuminoids showed antibacterial photodynamic effects (>3 log reduction of CFU) against Escherichia coli and Staphylococcus aureus upon blue light illumination. In contrast to natural curcumin, effective photokilling of E. coli was possible without the addition of permeabilizing agents. Ten micromolar of the most active compound (8) achieved a 7 log decrease of E. coli after light activation with a fluence of 33.8 J/cm, whereas S. aureus was inactivated by more than 4 log at a fluence of 5.3 J/cm. Overall the reduction in bacterial count was at least 100-fold more effective with these new curcuminoids in comparison to natural curcumin.
天然存在的光敏剂姜黄素具有极好的生物相容性，但由于以下原因，其抗菌光动力疗效受到限制：（i）对革兰氏阴性菌细胞壁的黏附性弱，（ii）（光）稳定性低，以及（iii）在水中的溶解度有限。在这项研究中，通过不同的合成路线制备了带有正电荷取代基的新型姜黄素衍生物。这些衍生物具有极好的水溶性、提高的光稳定性和低聚集性。所有新型姜黄素衍生物在蓝光照射下均表现出针对大肠杆菌和金黄色葡萄球菌的抗菌光动力效应（CFU 减少>3 对数）。与天然姜黄素不同，新型姜黄素可在不添加通透剂的情况下有效杀灭大肠杆菌。最活跃的化合物（8）的浓度为 10 μM 时，在 33.8 J/cm 的光辐照下，大肠杆菌的数量减少了 7 对数，而在 5.3 J/cm 的光辐照下，金黄色葡萄球菌的数量减少了 4 对数以上。总的来说，与天然姜黄素相比，这些新型姜黄素在减少细菌数量方面的效果至少提高了 100 倍。
