Hematoporphyrin-Derived Soluble Porphyrin−Platinum Conjugates with Combined Cytotoxic and Phototoxic Antitumor Activity
| Autor: | Günther Bernhardt, Karl-Christian Bart, Christian Lottner, Henri Brunner |
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| Rok vydání: | 2002 |
| Předmět: |
Male
Light Organoplatinum Compounds Stereochemistry Carboxylic acid chemistry.chemical_element Antineoplastic Agents Ligands Structure-Activity Relationship chemistry.chemical_compound Drug Discovery Tumor Cells Cultured Humans Photosensitizer Aged Chelating Agents Hematoporphyrin chemistry.chemical_classification Photosensitizing Agents Ligand Biological activity Middle Aged Combinatorial chemistry Porphyrin Hematoporphyrins chemistry Molecular Medicine Female Drug Screening Assays Antitumor Platinum Ethylene glycol |
| Zdroj: | Journal of Medicinal Chemistry. 45:2064-2078 |
| ISSN: | 1520-4804 0022-2623 |
| Popis: | To combine the cytotoxic activity of cisplatin and the phototoxicicity of hematoporphyrin derivatives in the same molecule, hematoporphyrin was derivatized at the two secondary alcohol positions by etherification with oligo- and poly(ethylene glycol) units. The two carboxylic acid groups of the propionate side chains were used to bind platinum fragments. The antiproliferative activity of 35 platinum complexes (0.5, 1, and 5 microM) differing in solubility and type of the platinum fragment and the corresponding porphyrin ligands were studied in tests with TCC-SUP and J82 transitional bladder cancer cells in the dark and after irradiation (lambda = 600-730 nm, 24 J/cm(2)). The most active compounds were found among the porphyrin-platinum conjugates bearing the diammine and (RR/SS)-trans-1,2-diaminocyclohexane ligand. These porphyrin-platinum conjugates, especially the water-soluble species, such as diammine(7,12-bis[1-(poly(ethylene glycol)-750-monomethyl ether-1-yl)ethyl]-3,8,13,17-tetramethylporphyrin-2,18-dipropionato)platinum(II), are promising candidates for the development of a novel type of photosensitizers with intrinsic cytotoxicity, which due to the porphyrin constituent may selectively enrich in tumor tissues. |
| Databáze: | OpenAIRE |
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