Structure-activity relationship of porphyrin-induced photoinactivation with membrane function in bacteria and erythrocytes

• Published in: Photochemical & photobiological sciences Vol. 17; no. 7; pp. 954 - 963
• Main Authors: Kato, Hisato, Komagoe, Keiko, Inoue, Tsuyoshi, Masuda, Kazufumi, Katsu, Takashi
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 2018; Royal Society of Chemistry
• Subjects: Acetylcholinesterase; Animals; Anti-Bacterial Agents - pharmacology; Bacteria; Biochemistry; Biomaterials; Cattle; Chemistry; Erythrocyte Membrane - drug effects; Erythrocytes; Erythrocytes - cytology; Erythrocytes - drug effects; Hemoglobin; Humans; Inhibition; Irradiation; Leakage; Lysis; Membrane potential; Membrane Potentials - drug effects; Microbial Viability - drug effects; Morphology; Octanol-water partition coefficients; Photoinactivation; Photosensitizing Agents - pharmacology; Physical Chemistry; Plant Sciences; Porphyrins; Porphyrins - pharmacology; Potassium; Protoporphyrin; Radiation; Staphylococcal Infections - drug therapy; Staphylococcus aureus - cytology; Staphylococcus aureus - drug effects; Structure-Activity Relationship
• ISSN: 1474-905X; 1474-9092
• 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. We analyzed the structure-activity relationship of natural porphyrins and the related analogs with the photoinactivation of membrane function in bacteria and erythrocytes.