Department of Chemistry, Pomona College, 645 North College Avenue, Claremont, California 91711, United States.
J Med Chem. 2013 Feb 28;56(4):1491-8. doi: 10.1021/jm3016798. Epub 2013 Feb 14.
Combination therapy of cisplatin with flavonols is a promising treatment for increasing the efficacy of cisplatin when combating cancer. However, little is known about the molecular interactions between cisplatin and flavonols. The data herein helps to elucidate this interaction. Spectrophotometric data in the UV-visible range indicates that hydroxyl groups on the B-ring of flavonols are essential for reactivity with cisplatin. The use of a quartz crystal microbalance with dissipation monitoring approach clearly supports the critical role played by B-ring hydroxyls in their interactions with a cisplatin-bound double-stranded DNA surface; an increase in the number of hydroxyl groups on the B-ring of flavonols parallels the increase in their reaction rates with cisplatin and correlates well with their reported effects on leukemia cell apoptosis efficacy. This study underscores the importance of B-ring hydroxyls in cisplatin's toxicity and may be used to better understand and improve combination therapies of flavonols with cisplatin.
顺铂与类黄酮联合治疗是提高顺铂抗癌疗效的一种很有前途的治疗方法。然而，人们对顺铂与类黄酮之间的分子相互作用知之甚少。本文中的数据有助于阐明这种相互作用。紫外-可见分光光度数据表明，类黄酮 B 环上的羟基对于与顺铂的反应至关重要。利用石英晶体微天平与耗散监测法清楚地支持了 B 环羟基在与顺铂结合的双链 DNA 表面相互作用中所起的关键作用；类黄酮 B 环上羟基数量的增加与它们与顺铂的反应速率的增加平行，并与它们对白血病细胞凋亡疗效的报道结果很好地相关。这项研究强调了 B 环羟基在顺铂毒性中的重要性，并可用于更好地理解和改善类黄酮与顺铂的联合治疗。
