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Implications and problems in analysing cytotoxic activity of hydroxyurea in combination with a potential inhibitor of ribonucleotide reductase

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Summary

The cytotoxicity of hydroxyurea in combination with 2,2′-bipyridyl-6-carbothioamide (a potential inhibitor of ribonucleotide reductase) on P388 murine leukemia is reported. Synergistic activity was studied using various interpretations of the isobologram method and the combination index method. We evaluated the pros and cons of these methods and their overall usefulness. In our opinion, to obtain all possible information from a compound association, it is important to choose a formally correct method that (a) can quantitatively evaluate synergism or antagonism, (b) may offer the possibility of averaging final results, (c) needs a minimal amount of experimental data, and (d) is rapid. Moreover, we emphasize both the utility of testing at least three molar ratios of compound association and the importance of carefully choosing the fractional inhibition used in calculating the combination effect. Such evaluation of drug combinations gives information essential to the preparation of new anticancer drug regimens and to the early assessment of biochemical interactions.

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Authors and Affiliations

  1. Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Via del Giochetto, I-06100, Perugia, Italy

    Giuseppe Nocentini & Anna Barzi

  2. Department of Chemical Sciences, University of Camerino, Via S. Agostino, I-62032, Camerino, Italy

    Palmarisa Franchetti

Authors
  1. Giuseppe Nocentini
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  2. Anna Barzi
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  3. Palmarisa Franchetti
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Additional information

Supported in part by MPI (40%) and CNR (Special Project Oncology) contract 8702684.44

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Nocentini, G., Barzi, A. & Franchetti, P. Implications and problems in analysing cytotoxic activity of hydroxyurea in combination with a potential inhibitor of ribonucleotide reductase. Cancer Chemother Pharmacol 26, 345–351 (1990). https://doi.org/10.1007/BF02897291

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  • DOI: https://doi.org/10.1007/BF02897291

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