School of Pharmacy, Shujitsu University, 1-6-1 Nishigawara, Naka-ku, Okayama-shi, Okayama 703-8516, Japan.
Photochem Photobiol Sci. 2018 Jul 11;17(7):954-963. doi: 10.1039/c8pp00092a.
We analyzed the structure-activity relationship of porphyrins with the photoinactivation of membrane function in bacteria and erythrocytes. The porphyrins tested were protoporphyrin (PP), mesoporphyrin (MP), deuteroporphyrin (DP), hematoporphyrin (HP), coproporphyrin (CP) and uroporphyrin (UP), along with hematoporphyrin derivative (HPD) and photofrin (PF). These porphyrins dissipated membrane potential of Staphylococcus aureus cells depending on the degrees of respiratory inhibition and K+ leakage. The dysfunction of bacterial membrane was caused within minutes and in the order of PP ∼ MP > DP > HPD ≫ HP > PF > CP ∼ UP. For bovine erythrocytes, these porphyrins induced leakage of K+ and inhibition of the enzyme acetylcholinesterase, which is located on the outer layer of the erythrocyte membrane, in the same order as that observed in bacteria. At high concentrations of PP, MP, DP and HPD, hemolysis (the lysis of erythrocytes with liberation of hemoglobin) was also induced. We found that the degree of photoinactivation of membrane function was closely associated with porphyrin-induced morphological changes in bovine erythrocytes, forming a crenated form from the normal discoid, which is the index of the amount of porphyrins in the outer layer of the cytoplasmic membrane. Furthermore, the degree of morphological changes was related with the octanol/water partition coefficients of porphyrins. These results strongly supported that porphyrins located in the outer layer of cytoplasmic membrane inactivated the cell membrane function by photo-irradiation, and the strength of photoinactivation by porphyrins depended on their affinity to the cell membrane.
我们分析了卟啉类化合物的结构-活性关系及其对细菌和红细胞膜功能的光灭活作用。测试的卟啉类化合物有原卟啉（PP）、中卟啉（MP）、次卟啉（DP）、血卟啉（HP）、粪卟啉（CP）和尿卟啉（UP），以及血卟啉衍生物（HPD）和血卟啉单甲醚（PF）。这些卟啉类化合物会根据呼吸抑制和 K+泄漏的程度耗散金黄色葡萄球菌细胞的膜电位。细菌膜的功能障碍在数分钟内发生，且按 PP∼MP>DP>HPD≫HP>PF>CP∼UP 的顺序出现。对于牛红细胞，这些卟啉类化合物以与在细菌中观察到的相同顺序诱导 K+泄漏和位于红细胞膜外层的酶乙酰胆碱酯酶的抑制。在高浓度的 PP、MP、DP 和 HPD 下，也会诱导红细胞溶血（即红细胞破裂并释放血红蛋白）。我们发现，膜功能的光灭活程度与卟啉诱导的牛红细胞形态变化密切相关，从正常的圆盘状形成锯齿状，这是质膜外层卟啉数量的指标。此外，形态变化的程度与卟啉的辛醇/水分配系数有关。这些结果有力地支持了卟啉类化合物位于细胞质膜外层，通过光照射使细胞膜功能失活，并且卟啉的光灭活强度取决于它们与细胞膜的亲和力。
