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New approach for screening anti-tumor compounds

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Chinese Science Bulletin

Abstract

A new screening approach for anticancer active compounds is presented. In this method, a target enzyme is incubated with a mixture of compounds, and then the complex formed by the target and small molecules is separated from the rest of the mixture by ultra-filtration. The complex that is retained on the membrane is subsequently washed with acid and small molecules that are specifically bound to the target are released and collected, then analyzed by highperformance liquid Chromatograph combined with electrospray ionization mass spectrometry (HPLC/ESI-MS) analysis. We have successfully applied this method to screen anticancer compounds. DNA topoisomerase II is used as a target to capture anti-tumor candidates from a mixture of combinatorial compounds, such as doxorubicin, daunorubicin and pravastain.

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References

  1. Terrett, N. K., Gardner, M., Gordon, D. W. et al., Combinatorial synthesis—The design of compound libraries and their application to drug discovery, Tetrahedron, 1995, 51: 8135–8173.

    Article  Google Scholar 

  2. Gordon, E. M., Gallop, M. A., Campbell, D. et al., Combinatorial organic synthesis: Applications to drug discovery, Eur. J. Med. Chem., 1995, 30: 337s–348s.

    Google Scholar 

  3. Li, Y. Y., Li, Z. Y., Wang, H. et al., Topoisomerases and anticancer drugs, Pharmaceutical Advance (in Chinese), 1996, 20(3): 138–142.

    Google Scholar 

  4. Nicholas, R. C., DNA gyrase and the supercoiling of DNA, Science, 1980, 207: 953.

    Article  Google Scholar 

  5. Lock, R. B., Ross, W. E., DNA topoisomerases in cancer therapy, Anti-cancer drug design, 1987, 2: 151–154.

    Google Scholar 

  6. Liu, C. C., Xie, B. F., Pan, Q. C., The relationship of DNA intercalative agents and inhibitors of DNA topoisomerase II and antitumor—Introducing two methods for antitumor drug screening, Cancer (in Chinese), 1991, 10(3): 215–219.

    Google Scholar 

  7. Liu, X. M., Wang, L. G., Ji, X. J., Determination of DNA topoisomerase II from mouse leukemia L1210 cells as target for screening antitumor agents, Cancer (in Chinese), 1991, 10(3): 220–225.

    Google Scholar 

  8. Wllison-lingard, L., Davis, P. W., Ecker, D. J. et al., Deconvolution of combinatorial libraries for drug discovery: Experimental comparison of pooling strategies, J. Med Chem., 1996, 39: 2720–2726.

    Article  Google Scholar 

  9. Gallop, M. A., Barrett, R. W., Dower, W. J. et al., Applications of combinatorial Technologies to drug discovery, 1. Background and peptide combinatorial Libraries, J. Med. Chem., 1994, 37: 1233–1251.

    Article  Google Scholar 

  10. Eric, G., Zhuang, S., Benjamin, E. et al., Methionine aminopeptidas (type 2) is the common target for angiogensis inhibitors AGM-1470 and ovalicin, Chem. & Biol., 1997, 4(6): 461–771.

    Article  Google Scholar 

  11. Randall, W. N., Jennifer, R. K., Allan, L. B. et al., Mass spectrometric Immunoassay, Anal. Chem., 1995, 67: 1153–1158.

    Article  Google Scholar 

  12. Brummel, C. L., Vickerman, J. C., Carr, S. A. et al., Evaluation of mass spectrometric methods applicable to the direct analysis of non-peptide bead-bound combinatorial libraries, Anal. Chem., 1996, 68: 237–242.

    Article  Google Scholar 

  13. Wu, D. L., Li, M. J., Gao, H. Z. et al., Doxorubicin—albumin conjugate reverses resistance in multidrug resistant KB/VCR cells to daunorubicin, Chinese Journal of Pharmacology and Toxicology, 1997, 11(1): 54–58.

    Google Scholar 

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Correspondence to Yuanjiang Pan.

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Pan, Y., Zhang, H. & Chen, Y. New approach for screening anti-tumor compounds. Chin.Sci.Bull. 48, 630–633 (2003). https://doi.org/10.1007/BF03325643

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  • DOI: https://doi.org/10.1007/BF03325643

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