Spectroscopic evidence for anthracenedione antineoplastic agent self-association and complex formation with flavin nucleotides.

Journal Article (Journal Article)

Dihydroxyanthraquinone (DHAQ) and ametantrone (anthraquinone) are two new anthracenedione antineoplastic agents which were found by proton NMR spectroscopy to self-associate in aqueous media. Self-association was consistent with a bimolecular model, with average association constant values of 3400 and 2900 M-1 determined for DHAQ and ametantrone, respectively. Both anthracenediones interacted with the flavin nucleotides FMN and FAD to produce concentration-dependent upfield shifts of the flavin isoalloxazine ring proton signals, as observed by proton NMR spectroscopy. Average association constant values obtained for FMN-DHAQ, FAD-DHAQ, FMN-ametantrone, and FAD-ametantrone complexation were 5100, 2600, 4300, and 1600 m-1, respectively. Optical difference spectroscopy confirmed FMN-DHAQ complexation, which resulted in a hyperchromic, bathochromic shift of the DHAQ spectrum following addition of FMN. These results were consistent with the formation of a pi-pi bimolecular ring-stacking complex. Information obtained on anthracenedione self-association and complexation with flavins may be of consequence in the interpretation of anthracenedione-DNA binding data and flavoprotein-mediated anthracenedione metabolic activation.

Full Text

Duke Authors

Cited Authors

  • Kharasch, ED; Novak, RF

Published Date

  • November 1, 1984

Published In

Volume / Issue

  • 234 / 2

Start / End Page

  • 497 - 512

PubMed ID

  • 6497384

International Standard Serial Number (ISSN)

  • 0003-9861

Digital Object Identifier (DOI)

  • 10.1016/0003-9861(84)90297-2

Language

  • eng

Conference Location

  • United States