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PHOTO‐INDUCED OXIDATIVE ACTIVATION OF THE ANTITUMOR DRUG 2N‐METHYL‐9‐HYDROXYELLIPTICINIUM IN VITRO
Author(s) -
Auclair Christian
Publication year - 1987
Publication title -
photochemistry and photobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.818
H-Index - 131
eISSN - 1751-1097
pISSN - 0031-8655
DOI - 10.1111/j.1751-1097.1987.tb08402.x
Subject(s) - chemistry , singlet oxygen , superoxide , dabco , covalent bond , superoxide dismutase , adduct , nucleophile , photochemistry , reactive oxygen species , oxidative phosphorylation , in vitro , oxygen , stereochemistry , medicinal chemistry , oxidative stress , biochemistry , organic chemistry , octane , enzyme , catalysis
— The phenolic antitumor drug 2N‐methyl‐9‐hydroxyellipticine (NMHE) has been found to undergo oxidative activation upon irradiation with near‐UV light at 365 nm (UVA) in aqueous medium. In the presence of leucine used as biological nucleophile, UVA‐induced activation of NMHE results in covalent binding as shown by the generation of the corresponding adduct isobutyl‐oxazolopyridocarbazole (IB‐OPC). The reaction involves as the initial step the one‐electron transfer from the drug to molecular oxygen yielding superoxide anion (O 2 ‐ ) whereas the generation of IB‐OPC may proceed either through a free radical reaction or a Michael addition reaction. The UVA light‐induced production of IB‐OPC is markedly increased by superoxide dismutase (SOD) and by the singlet oxygen quencher diazabicyclooctane (DABCO) but not affected by β‐carotene. It is concluded that UVA induces the oxidation of NMHE through an oxidasic process which may result in the covalent binding of the drug to biological nucleophiles. This finding leads to further investigation of the photodynamic action of NMHE in tumor cells.