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

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

Pubmed Central 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