benzoporphyrin-d and Hemolysis

Benzoporphyrin derivative (BPD) is a potent photosensitizer in biological systems. There are four structural analogues of BPD. The analogues share the same chromophor, which results in their having almost identical optical spectra, extinction coefficients, and yields of singlet oxygen. Small structural differences affect their photosensitizing potency in various biological systems, and thus make them an interesting tool to study the structure-activity relationship. The ranking of the photosensitizing potency of the analogues differed depending on the test system. The more efficient photosensitization of tumor cell lines by the highly lipophilic monoacids as compared to that by less lipophilic diacids correlated positively with the partition coefficient, and was related to the rate of diffusion into the cells. However, in the assay systems where PDT targets were located in the membrane (red blood cells hemolysis, enveloped vesicular stomatitis virus, isolated mitochondria) there was very little difference in photosensitizing potency of BPD analogues. The results indicate that the evaluation of photosensitizers is affected by the test system and thus for photosensitizers screening purposes, the choice of the test system should be made based on the intended ultimate use.

Topics: Animals; Cattle; Drug Evaluation; Hemolysis; Humans; Mice; Mitochondria, Liver; Oxidative Stress; Oxygen; Photosensitizing Agents; Porphyrins; Rats; Singlet Oxygen; Structure-Activity Relationship; Tumor Cells, Cultured; Vesicular stomatitis Indiana virus

The ability of a photosensitizer to partition into membrane is determined by its structure and physical properties. Partitioning behavior can be quantitated as the partition coefficient (Kp) for a particular drug. This property may be an important determinant of cytocidal efficacy in photodynamic therapy. The Kp of five photoactive drugs--13,17-ditetraammonium protoporphyrin (PH1008), photofrin II (PII), hematoporphyrin (Hp), benzoporphyrin derivative monoacid (BPD-MA), coproporphyrin (Cp), and uroporphyrin (Up)--was determined using a simple liposome system composed of sonicated egg phosphatidylcholine single bilayer vesicles. The cytocidal efficacy of each drug was compared by determining the concentration of drug resulting in 50% maximal lysis (C50) obtained by measuring the hemoglobin absorbance at 414 nm released from lysed human red blood cells. The percentage lysis at 1 microM final drug concentration was also determined. An argon-dye laser was used to administer light of 630-nm wavelength for a total exposure of 5 J/cm2. Porphyrins with a greater tendency to partition into phosphocholine bilayer membranes demonstrated a greater lytic efficacy in the rbc system utilized. The comparison of physical properties with lytic ability may be useful in understanding the mechanism by which PDT exerts its effects and in predicting the clinical efficacy of different drugs.

Topics: Cell Membrane; Coproporphyrins; Dihematoporphyrin Ether; Erythrocytes; Hematoporphyrin Photoradiation; Hematoporphyrins; Hemoglobins; Hemolysis; Humans; Laser Therapy; Phosphatidylcholines; Photochemotherapy; Porphyrins; Protoporphyrins; Radiation-Sensitizing Agents; Uroporphyrins