Chemical, Biologic and Biophysical Studies on ‘Hematoporphyrin Derivative’

Kessel, David; Chang, C. K.; Musselman, Brian

doi:10.1007/978-1-4613-2165-1_24

Cited by 54 publications

(28 citation statements)

References 12 publications

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“…As can be seen from the chromatographic data (Fig. 4) and as shown by others (Moan & Sommer, 1981;Kessel & Chou, 1983;Dougherty et al, 1984;Margalit et al, 1985;Swincer et al, 1985;Kessel et al, 1985;Kessel, 1986b;Dougherty, 1987;Kessel et al, 1987a,b;Bryne et al, 1987), current preparations of such species are non-homogeneous in size. Hence our use of the term 'dominant size'.…”

Section: Binding Of Hvd Monomers To Hsasupporting

confidence: 74%

“…The porphyrin preparations currently employed in PDT, such as HPD, Pf, DHE and HPE, are complex porphyrin mixtures (Moan & Sommer, 1981;Kessel & Chou, 1983;Dougherty et al, 1984;Margalit et al, 1985;Swincer et al, 1985;Kessel et al, 1985;Kessel, 1986b;Dougherty, 1987;Kessel et al, 1987a,b;Bryne et al, 1987;Potter et al, 1987). In general, these preparations contain two types of species: (a) well-defined porphyrins such as HP, HVD (two isomers) and PP, each of which can be present as an equilibrium mixture of monomers and reversible aggregates (Brown & Shillcock, 1976;Karns et al, 1979;Brown et al, 1980;Margalit & Rotenberg, 1984;Margalit et al, 1985;Cohen & Margalit, 1986); (b) irreversible aggregates, which are not well-defined and are porphryin clusters distinguished by the following properties (Moan & Sommer, 1981;Grossweiner & Goyal, 1984;Dougherty et al, 1984;Margalit et al, 1985;Swincer et al, 1985;Dougherty, 1987;Kessel et al, 1987a,b;Bryne et al, 1987;Potter et al, 1987) In previous papers Rotenberg et al, 1987) we have reported on the thermodynamics of binding of monomers and reversible dimers of DP, HP and PP to serum albumin.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Binding of porphyrin to human serum albumin. Structure–activity relationships

Cohen

Margalit

1990

Biochemical Journal

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Section: Binding Of Hvd Monomers To Hsasupporting

confidence: 74%

Section: Introductionmentioning

confidence: 99%

Binding of porphyrin to human serum albumin. Structure–activity relationships

Cohen

Margalit

1990

Biochemical Journal

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“…in the order di-methyl ether, di-ethyl ether, di-propyl ether, dibutyl ether and di-amyl ether. Haematoporphyrin di-amyl ether was more efficient than haematoporphyrin derivative and insignificantly less efficient than photofrin II (DHE (Bonnett & Berenbaum, 1983;Kessel et al, 1985). Neither is it known why certain components of these porphyrin preparations are selectively retained by tumours compared with many normal tissues.…”

mentioning

confidence: 99%

“…So far several promising reports on the efficacy of this treatment have been published (Dougherty, 1985 and references cited therein). The complete chemical composition of the active fraction of HpD and DHE has not been finally resolved, although it has been proposed that it consists of dihematoporphyrin ethers or esters (Bonnett & Berenbaum, 1983;Kessel et al, 1985). Neither is it known why certain components of these porphyrin preparations are selectively retained by tumours compared with many normal tissues.…”

mentioning

confidence: 99%

Photodynamic therapy of C3H mouse mammary carcinoma with haematoporphyrin di-ethers as sensitizers

Evensen¹,

Sommer²,

Rimington³

et al. 1987

Br J Cancer

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Summary Haematoporphyrin di-ethers were synthesized and tested as sensitizers for photodynamic therapy of C3H/Tif mammary tumours in mice. Growth curves of the tumours were determined by measuring the tumour volume. The animals were given 25 mg porphyrins kg-1 body weight i.p. and 24 h later exposed to 135 Jcm-2 of 630 nm light at a fluence rate of 150 mW cm-2. The sensitizing efficiency of the ethers was measured in terms of the increase in growth time of the treated tumours, as compared with that of untreated controls, needed to reach a volume 5 times larger than that at the time of the treatment. This sensitizing efficiency increased with decreasing polarity, i.e. in the order di-methyl ether, di-ethyl ether, di-propyl ether, dibutyl ether and di-amyl ether. Haematoporphyrin di-amyl ether was more efficient than haematoporphyrin derivative and insignificantly less efficient than photofrin II (DHE (Bonnett & Berenbaum, 1983;Kessel et al., 1985). Neither is it known why certain components of these porphyrin preparations are selectively retained by tumours compared with many normal tissues. It has been assumed that polarity and aggregation properties may play important roles (Moan, 1986). This led us to prepare and test several porphyrin di-ethers with chromatographic properties, and hence polarities, in the range of those of the tumourlocalizing fraction of HpD and DHE. These compounds have a known chemical structure and with one exception we found that they could be purified to the degree desired. It is a major drawback for the clinical and experimental use of HpD and DHE that they contain so many chromatographically different components (Bonnett et al., 1980; Hp di-ethers were prepared by a modification of the procedures described by Kuster and Deihle (1913) and Willstatter and Fischer (1913): Hemin (Sigma Chem. Co.) was dissolved in HBr/acetic acid (specific gravity 1.14, 33%) and allowed to stand for 4h. After removal of the solvent under reduced pressure, methanol, ethanol, propanol, butanol, amyl alcohol or hexanol was added and allowed to react for 24h at 50°C. The resulting porphyrins have ether groups at the 2-and 4-positions of the ring and ester groups at the 6-and 7-positions (see Figure 1). The latter groups were removed by treatment with KOH in tetrahydrofuran. The methyl-, ethyl-, propyl-, and butyl-ethers were >90% pure as analyzed by HPLC. Separate runs of each ether were performed, as well as runs of mixtures of all of them to determine their relative retention times. The relation of the retention time to the number of carbon atoms in the substituting alcohol was practically linear (Rimington et al., 1986). In the chromatogram of the amyl-ether two slightly separated peaks appeared (ret. times 30 and 31 min, respectively) related to the fact that commercial amyl alcohol is a mixture of -87% iso-amyl alcohol and 13% amyl alcohol. By the present method it was not possible to prepare the hexyl-ether more than 50% pure. Two major porphyrin contaminants of unknown structure (ret.

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“…Ester bonds hydrolyze in aqueous base, whereas ether bonds are stable. Using this information, with additional evidence, Kessel et al 9 proved the predominance of ester-linked porphyrins. Byrne et al 1 helped resolve the discrepancy between ether and ester bond linkages in Photofrin by comparing the method of preparation of the hematoporphyrin diacetate.…”

Section: Photofrinmentioning

confidence: 94%