Elucidation of the molecular interaction between cisplatin and flavonol(s) and their effect on DNA binding.

Document Type

Article

Publication Date

2-28-2013

Publication Title

Journal of medicinal chemistry

Keywords

washington; spokane; Antineoplastic Agents; Cisplatin; DNA; Flavonols; Hydroxylation; Quartz Crystal Microbalance Techniques; Quercetin; Spectrophotometry

Abstract

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.

Clinical Institute

Cancer

Clinical Institute

Cardiovascular (Heart)

Department

Cardiology

Department

Oncology

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