Soluble tetraarylporphyrin-platinum conjugates as cytotoxic and phototoxic antitumor agents.
A series of asymmetric tetraarylporphyrins was synthesized from pyrrole, para-substituted oligo- or poly(ethylene glycol) monomethyl ether benzaldehyde and from 4-hydroxybenzaldehyde etherified with diethyl bromomalonate according to the Lindsey method. After hydrolysis of the tetraarylporphyrin esters, the resulting carboxylic acid groups were used to bind platinum fragments. In comparison to analogous hematoporphyrin-platinum conjugates, the title compounds are characterized by a 30 nm bathochromic shift of their absorption bands. The antiproliferative activity of 18 platinum complexes (1, 5, and 10 microM) differing in solubility, type of the platinum fragment, and the corresponding tetraarylporphyrin ligands were studied on TCC-SUP transitional bladder cancer cells in the dark and after irradiation (lambda = 600-730 nm; 24 J/cm(2)). The most active compounds were among the tetraarylporphyrin-platinum conjugates bearing the diammine and (RR/SS)-trans-1,2-diaminocyclohexane ligands.
Lottner
Christian
C
Institut für Anorganische Chemie and Institut für Pharmazie, Universität Regensburg, 93040 Regensburg, Germany.
Bart
Karl-Christian
KC
Bernhardt
Günther
G
Brunner
Henri
H
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002614:Chelating Agents / Q000138:chemical synthesis* / Q000737:chemistry; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008024:Ligands; D008027:Light; D009944:Organoplatinum Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D017319:Photosensitizing Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011166:Porphyrins / Q000138:chemical synthesis* / Q000737:chemistry; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D002614:Chelating Agents; D008024:Ligands; D009944:Organoplatinum Compounds; D017319:Photosensitizing Agents; D011166:Porphyrins