Hematoporphyrin 11 derivative

The development of so-called photodynamic therapy uses lasers for treatment of cancer. The patient is injected with a substance called hematoporphyrin derivative [68335-15-9] which is preferentially localized in cancerous tissues. The patient is later irradiated with laser light, often with a dye laser at a wavelength around 630 nm. The light energy catalyticaHy photooxidizes the hematoporphyrin derivative, releasing materials which kill the nearby cancerous tissue. Normal tissue which did not retain the chemical is not harmed. Photodynamic therapy offers promise as a new form of cancer treatment. 

Various dyes can be used as photosensitizers, including methylene blue, riboflavine, and hematoporphyrin derivative. The selection of the photosensitizer should be in favor of a compound that exclusively leads to Reaction (b), so that a clear interpretation of the results is possible. 

The new derivatives 121a (A-C) and 122a (A-C) were evaluated for their photocytotoxic activities in comparison with Photofrin , the commercial anti-cancer hematoporphyrin derivative formulation. Compounds 121a (A-C) have revealed to be more PDT efficient than Photofrin , but surprisingly compounds 122a (A-C) have shown to be inactive. 

Hematoporphyrin derivative or Photofrin was the first PS to be studied in detail. However, it proved highly frustrating for scientists who attempted to determine its chemical structure and to identify its components (Kessel, 1986, 1989b Kessel and Thompson, 1987 Kessel et al., 1987a, b). There was significant variation between batches and attempts to fractionate it into its individual component molecules frequently yielded mixtures as complicated as the starling material (Kessel, 1982, 1989a). 

Kessel D (1982) Components of hematoporphyrin derivatives and their tumor-localizing capacity. Cancer Res 42 1703-1706. 

Kessel D, Thompson P (1987) Purification and analysis of hematoporphyrin and hematoporphyrin derivative by gel exclusion and reverse-phase chromatography. Photochem Photobiol 46 1023-1025. 

Kessel D, Thompson P, Musselman B, Chang CK (1987a) Chemistry of hematoporphyrin-derived photosensitizers. Photochem Photobiol 46 563-568. 

Tanielian C, Schweitzer C, Mechin R, Wolff C (2001) Quantum yield of singlet oxygen production by monomeric and aggregated forms of hematoporphyrin derivative. Free Radical Biology and Medicine 30 208-212. 

Chemistry and Structure of the Principal Tumor-Localizing Porphyrin Photosensitizer in Hematoporphyrin Derivative... 

The principal tumor-localizing component of Hematoporphyrin Derivative (HPD) has been demonstrated to be dimeric and trimeric hematoporphyrins (HP) interconnected with ester groups. Synthetic analogs as well as model compounds are used in our study to conclude that the reaction conditions employed in the traditional HPD preparation promote a nucleophilic substitution of the acetate group of one HP-acetate molecule by an propionate anion of another HP molecule. The effect of solvent on the stability and structural conformation of the diporphyrin esters have also been examined by spectroscopic methods. 

Fast atom bombardment mass spectrometry (FAB MS), hematoporphyrin derivatives, 3 8,351f Fe(II) cytochrome c... 

Triptycene-anthraquinone, half wave potentials, 157f Tumor-localizing fraction, hematoporphyrin derivative, 3 8-350,3 9f Two-photon absorption, metallotetraphenyl-porphyrins, 219-230... 

El-Far, M. and Pimstone, N. (1984) Porphyrin Protoporphyrin Plasma Protein Interaction - The Metabolic Basis for Tumor Localization of Hematoporphyrin Derivative - A Preliminary Report... 

Lottner, C., Bart, K.-C., Bemhart, G., Brunner, H. (2002) Hematoporphyrin-Derived Soluble Porphyrin-Platinum Conjugates with Combined Cytotoxic and Phototoxic Antitumor Activity, J. Med. Chem. 45, 2064-2078. 

Lipson RL, Baldes EJ. The photodynamic properties of a particular hematoporphyrin derivative. Arch Dermatol 1960 82 508-16. 

Kim YS, Song R, Lee CO, Sohn YS. Synthesis and biological activity of novel platinum(II) complexes of glutamate to hydrophilic hematoporphyrin derivatives. Bioorg Med Chem Lett 2004 14 2889-92. 

II 000 cm-1). Nevertheless, the photophysics of lanthanide porphyrinates is attractive because it could be of great help in medicine. For instance, hematoporphyrin derivatives are known to accumulate in malignant tumours and are used in medical diagnosis and photodynamic therapy of cancer. It is noteworthy that the Yb(III) complex with meso-tetra(3-pyridyl)porphyrin displays a substantial quantum yield (1.4%) when inserted into micelles formed by the non-ionic surfactant Triton X-100, a medium that can be considered as a model for biological tissues. 

Photofrin (a mixture of hematoporphyrin derivatives including various dimers) and Foscan (H2TOHPC) are the most widely used sensitizers in oncologic PDT and are indicated for a variety of cancers 102,103). In vitro and in vivo studies reported for these sensitizers and for the new generation of bacteriochlorin... 

It should be noted here that there is a very wide latitude in the quality of the commercially available materials. Recently reported experiences with ferric hematoporphyrin derivatives are quite typical. In general, esters are better than the unesterified bases. For the blood-derived materials the usual order of quality goes deutero, hemato, and meso, with protoporphyrin the worst. For a well-defined preparation of natural porphyrins, it is always best to purify the starting material and to characterize it ° satisfactorily before carrying out any chemical modifications. 

Bellnier DA, Dougherty TJ. Membrane lysis in Chinese hamster ovary cells treated with hematoporphyrin derivative plus light. Photochem Photobiol 1982 36 43-7. 

In biological physics studies, we have measured the excitation intensity dependence of chlorophyll a/b fluorescence (17), anisotropy decay times of tryptophan in various environments (18). energy transfer in spinach ehloroplasts (19), and decay kinetics of hematoporphyrin derivative (20). 

Our group became involved in this area in 1972 by following up on a series of publications emanating from the Mayo Clinic and elsewhere in the 1960s, where it had been demonstrated that a crude mixture of porphyrins (hematoporphyrin derivative, Hpd), first prepared by Schwartz as reported... 

Figure 4. Absorption spectrum of hematoporphyrin derivative (Hpd) in saline and 10% serum in saline. Reprinted with permission from D. R. Doiron, Photophysics and dosimetry of photoradiation therapy, in Porphyrins in Tumor Therapy, Plenum Press, New York, 1984.

T. Kawauchi, in Lasers and Hematoporphyrin Derivative in Cancer, Y. Hayata and T. J. Dougherty, Eds., Igaku-Shoin, Tokyo, 1983, pp. 25-32. 

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