Chair and Department of Chemical Technology of Drugs, Poznan University of Medical Sciences, Rokietnicka 3, 60-806 Poznan, Poland.
Doctoral School, Poznan University of Medical Sciences, Bukowska 70, 60-812 Poznan, Poland.
Molecules. 2024 Sep 24;29(19):4536. doi: 10.3390/molecules29194536.
Over the past few years, numerous bacterial strains have become resistant to selected drugs from various therapeutic groups. A potential tool in the fight against these strains is antimicrobial photodynamic therapy (APDT). APDT acts in a non-specific manner by generating reactive oxygen species and radicals, thereby inducing multidimensional intracellular effects. Importantly, the chance that bacteria will develop defense mechanisms against APDT is considered to be low. In our research, we performed the synthesis and physicochemical characterization of curcumin derivatives enriched with morpholine motifs. The obtained compounds were assessed regarding photostability, singlet oxygen generation, aggregation, and acute toxicity toward prokaryotic cells in the Microtox test. The impact of the compounds on the survival of eukaryotic cells in the MTT assay was also tested (WM266-4, WM115-melanoma, MRC-5-lung fibroblasts, and PHDF-primary human dermal fibroblasts). Initial studies determining the photocytotoxicity, and thus the potential APDT usability, were conducted with the following microbial strains: , , , , and . It was noted that the exposure of bacteria to LED light at 470 nm (fluence: 30 J/cm) in the presence of quaternized curcumin derivatives at the conc. of 10 µM led to a reduction in survival of over 5.4 log.
在过去的几年中,许多细菌菌株对来自不同治疗组的选定药物产生了耐药性。抗菌光动力疗法(APDT)是对抗这些菌株的潜在工具。APDT 通过生成活性氧和自由基以非特异性方式起作用,从而诱导多维细胞内效应。重要的是,细菌产生针对 APDT 的防御机制的机会被认为很低。在我们的研究中,我们进行了富含吗啉基序的姜黄素衍生物的合成和物理化学特性研究。对获得的化合物进行了光稳定性、单线态氧生成、聚集和微毒试验中针对原核细胞的急性毒性评估。还测试了化合物对 MTT 测定中真核细胞存活的影响(WM266-4、WM115-黑色素瘤、MRC-5-肺成纤维细胞和 PHDF-原代人真皮成纤维细胞)。最初的研究确定了光细胞毒性,从而确定了 APDT 的潜在可用性,使用了以下微生物菌株: 、 、 、 、 。结果表明,在 470nm LED 光下(剂量:30 J/cm),存在浓度为 10 µM 的季铵化姜黄素衍生物时,导致 的存活减少超过 5.4 对数。