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Combinatorial Chemistry & High Throughput Screening


ISSN (Print): 1386-2073
ISSN (Online): 1875-5402

An Instrument-Based Screening Assay for DNA-Targeted Anticancer Drugs Using Resonance Light Scattering

Author(s): Zhanguang Chen, Guoliang Liu, Maohuai Chen, Xi Chen, Mingyao Wu and Xingtong Chen

Volume 13, Issue 5, 2010

Page: [383 - 392] Pages: 10

DOI: 10.2174/138620710791292949

Price: $65


DNA is a valid drug target for development of target-based therapeutics against cancer. Screening DNA-targeted anticancer drugs is a key process for the research and development of new anticancer drugs. The traditional anticancer drug screening methods, including animal experiments and cell-based screening assays, have unavoidable drawbacks. In this contribution, the new instrument-based screening assay for DNA-targeted anticancer drugs in vitro using resonance light scattering (RLS) technique was proposed. The experiments suggested that the increment of RLS intensity was directly proportional to the antitumor effect of anticancer drugs. Therefore, it was intuitive to obtain the sequence of the antitumor activity of four anticancer drugs without data processing as follows: mitoxantrone (MIT) > pirarubicin (PIR) > daunorubicin (DAU) > doxorubicin (DOX) by RLS screening spectra. Moreover, the apparent equilibrium constant (K) was 1.23 x 104, 2.22 x 104, 4.66 x 104 L/mol for DOX, DAU, and PIR, respectively. The inhibitory concentration 50 (IC50) was 0.148, 0.102, 0.025, 0.013 μmol/L for DOX, DAU, PIR, MIT, respectively. Therefore, the antitumor effect of four drugs was as follows: MIT > PIR > DAU > DOX, which was in good agreement with the result obtained from RLS screening assays. The mechanism between DNA and anthracycline drugs was investigated using UV-vis spectroscopy, fluorescence spectroscopy, and electrophoresis experiments. The proposed assay is a rapid, intuitive, and easy-to-conduct bioassay with good accuracy and reproducibility.

Keywords: Instrument-based screening, resonance light scattering, DNA-targeted, anticancer drug, anthracycline, apparent equilibrium constant, inhibitory concentration 50

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