Haukvik T, Bruzell E, Kristensen S, Tønnesen H H
University of Oslo, School of Pharmacy, Department of Pharmaceutics, P.O.Box 1068 Blindern, 0316 Oslo, Norway.
Pharmazie. 2011 Jan;66(1):69-74.
Curcumin, bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione, has potential as a photosensitiser for photodynamic treatment of localised superficial infections in e.g., the mouth or skin. The aim of the present study was to evaluate the in vitro antibacterial phototoxic potential of a series of five curcumin derivatives. The gram-positive Enterococcus faecalis and the gram-negative Escherichia coli were used as bacterial models. The bacteria were exposed to curcuminoid preparations in two concentrations (2.5 and 25.0 microM) in combination with a constant irradiation dose (5 J/cm2). The UV-VIS absorption spectrum of the curcuminoids was in the same range as curcumin, 300-500 nm. Compound 1 (dimethoxycurcumin; C1) and compound 3 (bisdemethoxycurcumin; C3) were strongly phototoxic towards E. faecalis (no surviving bacteria) and showed a lower but significant effect towards E. coli (< or = 0.5 log reductions and 1 - 4 log reductions, respectively). Compound 2 (C2) and compound 4 (C4) in combination with blue light reduced the colony forming ability of E. faecalis (approximately 1-4 log reductions). The phototoxic effect of the curcuminoids varied with concentration, and for compounds C1, C2 and C3 it was further influenced by the addition of polyethylene glycol 400 (PEG 400) to the preparations. 2,6-Divanillylidenecyclohexanone (C5) showed very low phototoxic potential (< 0.2 log reductions) under the conditions used in the present study. The addition of polyethylene glycol 400 (PEG 400) seemed to increase the solubility of compound C1, C3 and C5 in phosphate buffered saline (PBS). This investigation demonstrates the importance and influence of the substituents on the phenolic rings and the keto-enol moiety for the phototoxic potential of curcumin and its derivatives.
姜黄素，双（4-羟基-3-甲氧基苯基）-1,6-庚二烯-3,5-二酮，有潜力作为光动力治疗局部浅表感染（如口腔或皮肤感染）的光敏剂。本研究的目的是评估一系列五种姜黄素衍生物的体外抗菌光毒性潜力。革兰氏阳性粪肠球菌和革兰氏阴性大肠杆菌被用作细菌模型。将细菌暴露于两种浓度（2.5和25.0微摩尔）的姜黄素类制剂中，并结合恒定的辐照剂量（5焦/平方厘米）。姜黄素类的紫外-可见吸收光谱与姜黄素在相同范围内，为300-500纳米。化合物1（二甲氧基姜黄素；C1）和化合物3（双去甲氧基姜黄素；C3）对粪肠球菌具有强烈的光毒性（无存活细菌），对大肠杆菌的影响较小但显著（分别为≤0.5个对数减少和1-4个对数减少）。化合物2（C2）和化合物4（C4）与蓝光联合使用可降低粪肠球菌的菌落形成能力（约1-4个对数减少）。姜黄素类的光毒性作用随浓度而变化，对于化合物C1、C2和C3，制剂中添加聚乙二醇400（PEG 400）会进一步影响其光毒性。在本研究使用的条件下，2,6-二香草亚基环己酮（C5）显示出非常低的光毒性潜力（<0.2个对数减少）。添加聚乙二醇400（PEG 400）似乎增加了化合物C1、C3和C5在磷酸盐缓冲盐水（PBS）中的溶解度。本研究证明了酚环和酮-烯醇部分上的取代基对姜黄素及其衍生物光毒性潜力的重要性和影响。
