Bacteriopurpurinimides:  Highly Stable and Potent Photosensitizers for Photodynamic Therapy

Abstract

The in situ conversion of the unstable bacteriochlorophyll a present in Rhodobacter sphaeroides produced highly stable bacteriopurpurin-18 which in a sequence of reactions was converted into a series of alkyl ether analogues of bacteriopurpurin-18-N-alkylimides with long wavelength absorption near 800 nm. The effective photosensitizers were found to localize in mitochondria but did not show any specific displacement of (3)H-PK11195, suggesting that the mitochondrial peripheral benzodiazepine receptor is not the cellular binding site for this class of compounds.

New Halogenated Water‐Soluble Chlorin and Bacteriochlorin as Photostable PDT Sensitizers: Synthesis, Spectroscopy, Photophysics, and in vitro Photosensitizing Efficacy

“…Tookad is derived from bacteriochlorophyll and, like most of the naturally occurring bacteriochlorins, is sensitive to oxygen, which results in rapid oxidation to the chlorin species. [31] In spite of the remarkable progress in PDT, the need for more efficient photosensitizers that are chemically pure, less phototoxic, have better localizing properties, and absorb light more intensely and deeper into the near-infrared, remains unfulfilled. The efficacy of PDT may be enhanced by combined therapies, while the photosensitizer specificity might be improved by various carrier-mediated targeting systems, [32] but the intrinsic photosensitizer properties remain a limiting factor for the widespread use of PDT for the treatment of cancer.…”

Efficient Synthesis and in vitro PDT Effect of Purpurin-18-N-Aminoimides

“…In other words the use of photosensitizer having long-wavelength band is desirable for better tissue penetration of excitied light in vivo, the purpurin-18-Naminoimides may be considered as promising candidates. 19,21 The in vitro activities of purpurin-18 methyl ester 5 and the corresponding purpurin-18-N-aminoimides were determined with A549 cells. A549 cells with each compound at variable concentrations were incubated in A549 cells at 37 o C for 3 h, 24 h and 48 h respectively.…”

“…Converting the six-membered anhydride ring of purpurin-18 into a six-membered cyclic imide structure was found to greatly increased wavelength absorption and good stability for the requirement of an improved photodynamic therapeutic agent. [10][11][12][13][14][15][16][17][18][19] Although previous report has described the synthesis of purpurin-18-N-(N,N-dimethyl)ethylimide from the chlorin p 6 . 14 However, the yield of the purpurinimide formed in this reaction was low.…”

The Translocator Protein as a Potential Molecular Target for Improved Treatment Efficacy in Photodynamic Therapy

“…These relatively unstable bacteriochlorins from Rhodobacter shaeroides were converted in situ into a series of stable N-hexylimide analogues 22-24 and tested in vitro and in vivo for their efficacy as PDT agents (Figure 9) [86]. The bacteriopurpurinimide 22 gave limited in vivo PDT efficacy in C3H mice bearing RIF tumors (drug dose 0.2 μmol.kg at 24 h post injection).…”