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The porphyrin handbook - Kadish K.M.

Kadish K.M. The porphyrin handbook - Academic press, 2000. - 368 p.
Download (direct link): kadishsmishgulilard2000.djvu
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Most early biological studies on Pc related to PDT were conducted with
water-soluble sulfonated metallo-phthalo-cyanines (MPcS). The effect of
the degree of sulphonation of MPcS on their PDT efficacy has been studied
in details both in vitro and in vivo. Brasseur et al. showed that the
mono- and disulphoated derivatives of Ga-, Al- and Zn(PcS)
are most active, whereas the tri- and tetra-sulphonated dyes are
inefficient sensitizers.353,354 In the same studies, Brasseur et al.354
have shown that the most hydrophilic isomer, with sulfonate groups at the
opposite positions of the Pc molecule, is completely devoid of
photocytotoxicity, whereas the most hydrophobic isomer, with sulfonate
substituents at adjacent benzene rings, is extremely efficient as a
photosensitizer in vitro. MPcS substituted with other biological
important functional groups such as amino, carboxyl, nitro, hydroxy and
neopentoxy groups, have been also evaluated for PDT. Meanwhile some
positively charged amino- and pyridino- Pc analogues as well as Zn(Pc)
analogues have also been studied.350-352
Brasseur et al. also reported the preparation as photosensitizers of
four Si(Nc) derivatives 476-479 with increasing lengths of aliphatic
chains.355 All these compounds induced tumor regression in at least 50%
of mice, whereas compound 477 gave a complete tumor response in 80% of
mice without apparent systemic toxicity at doses as high as 101/kg.
43 / Porphyrins as Photosensitizers in Photodynamic Therapy
213
Scheme 75. Vinylogous porphyrins.
Scheme 76. Glycosylated porphyrins.
214
Pandey and
Zheng
Scheme 77. Schematic representation of the four atropiosmers of a
glycosylated porphyrin where a means that the -OC(CH3)2- functon is
below, /i above the mean porphyrin plane.
Scheme 78. Water-soluble glycosylated porphyrins.
389 R =
V
Me
388

OH

4
390 R = ------OH

HO OH
XIV. Current Status of Photosensitizers Under Clinical Trials
The structures of porphyrin-based photosensitizers currently in clinical
trials are shown in Scheme 96.
Scotia Pharmaceuticals in Guildford, England has coordinated the
clinical trials on the H2(m-THPC), known
commercially as Foscan. The first clinical cases were those reported by
Ris et al. (1991) in which PDT with H2(m-THPC) was used after surgery in
four cases of malignant mesothelioma.356 The drug was delivered
intravenously as a solution in ethanol-polyethylene glycol 400-water
(2:3:5) at a dose of 0.3 mg / kg, with a drug-light interval of 48 hours
and a light dose of 10 J/cm2 (650 nm). Normal tissues were preserved even
when full-thickness tumor necrosis
43 / Porphyrins as Photosensitizers in Photodynamic Therapy
215
Scheme 79. Glycosylated porphyrins.
R
391 a,b : R1 = N02, R = OGIcAc
392 a,b : R1 = NH2, R = OGIcAc
393 a,b : R1 = NH-L-Ala-Fomc, R = OGIcAc
394 a,b : R1 = NH-L-Ala, R = OGIc
OAc
OGIcAc =
OGIc =
OAc
395 a,b : R1 = N02, R = OGIcAc
396 a,b : R1 = NH2, R = OGIcAc
397 a,b : R1 = NH-L-Ala-Fomc, R = OGIcAc
398 a,b : R1 = NH-L-Ala, R = OGIc
a and b refer to ortho and para positions, respectively
OAc
Scheme 80. Clycoconjugated meso-monoarylbenzochlorins.
OMe
(i) 3-(Dimethylamino)acrolein/POCl 3, (ii) CF3C02H/Ar, (iii) BBr^dry
CH2CI2, (iv) H2S04, (v) K2C03 in DMF/60 C, (vi) MeONa/MeOH.
216
Pandey and Zheng
Scheme 81. Glucose analogue of octaethylchlorin.
404 405
Scheme 82. Clycoconjugated tailor-made chlorins.
408 R-! = H, R2 = Heptyl
Scheme 83. Glycosylated porphyrins from protoporphyrin IX dimethyl ester.
OH
occurred. Some negative features included a mild skin photosensitivity
(which lasted about 14 days), loss of appetite, fluid retention, and
severe chest pain. In a phase-I clinical trial carried out by Ronn et
al?51 the half-life of the drug was found to be 45.4 hours across the
entire dose range. The ratio of tumor vs normal tissue was 2:3, and there
were no significant adverse effects. In 1996, Grosjean et al.35S
described PDT of 40 patients with early cancers of the esophagus and the
bronchi. Surface illumination of the tumor was performed 4 days after
intravenous injection of 0.15 mg/kg of m-THPC, using 652 or 514 nm
continuous
wave laser light. Twenty-seven patients (77%) showed no recurrence after
disease-free follow-ups that ranged from 3 to 38 months. Major
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