Kharasch E D, Novak R F
Arch Biochem Biophys. 1984 Nov 1;234(2):497-512. doi: 10.1016/0003-9861(84)90297-2.
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.
二羟基蒽醌（DHAQ）和氨甲蒽醌（蒽醌）是两种新型蒽二酮抗肿瘤药物，通过质子核磁共振光谱发现在水性介质中会发生自缔合。自缔合符合双分子模型，DHAQ和氨甲蒽醌的平均缔合常数分别测定为3400和2900 M-1。两种蒽二酮都与黄素核苷酸FMN和FAD相互作用，通过质子核磁共振光谱观察到黄素异咯嗪环质子信号出现浓度依赖性的高场位移。FMN-DHAQ、FAD-DHAQ、FMN-氨甲蒽醌和FAD-氨甲蒽醌络合的平均缔合常数分别为5100、2600、4300和1600 m-1。光学差示光谱证实了FMN-DHAQ的络合，加入FMN后，DHAQ光谱出现增色、红移。这些结果与π-π双分子环堆积络合物的形成一致。关于蒽二酮自缔合以及与黄素络合的信息，可能对解释蒽二酮与DNA的结合数据以及黄素蛋白介导的蒽二酮代谢活化具有重要意义。
