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Predicted binding rate of new cephalosporin antibiotics by a 3D-QSAR method: a new approach

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Abstract

Antibiotics are chemotherapeutic agents with activity against microorganisms, for example bacteria, fungi, or protozoa, used for the treatment of many types of diseases. Binding of antibiotics to serum proteins in human plasma is a major determinant of their pharmacodynamic and pharmacokinetic behavior and, consequently, can affect their systemic distribution in the body. Here, the predicted binding rates of ceftazidime and 13 other pharmacological agents classified as antibiotics to plasma proteins (percentage fraction bound; PFB) were evaluated by use of 3D-QSAR models. We attempted to establish the contribution of hydrogen bond donor/acceptor and hydrophobic properties supplied by electrostatic fields to the PFB. Significant cross-validated correlation q 2 (0.5–0.7) and the fitted correlation r 2 (0.7–0.97) coefficients revealed that these models have reasonable power to predict the design 19 new antibiotics using ceftazidime as template, these compounds being our suggestion for further studies.

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Acknowledgments

We thank the Romanian VIASAN program for financial support.

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Authors and Affiliations

  1. Department of Physiology and Biophysics, Faculty of Biology, University of Bucharest, Bucharest, Romania

    Speranta Avram & Dan Mihailescu

  2. Department of Medical Ambulatory, University of Medicine and Pharmacy “Victor Babes”, Timisoara, Romania

    Daniel Marius Duda-Seiman

  3. Department of Chemistry, Faculty of Chemistry-Biology-Geography, West University of Timisoara, Timisoara, Romania

    Corina Duda-Seiman & Florin Borcan

Authors
  1. Speranta Avram
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  2. Daniel Marius Duda-Seiman
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  3. Corina Duda-Seiman
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  4. Florin Borcan
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  5. Dan Mihailescu
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Correspondence to Speranta Avram.

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Avram, S., Duda-Seiman, D.M., Duda-Seiman, C. et al. Predicted binding rate of new cephalosporin antibiotics by a 3D-QSAR method: a new approach. Monatsh Chem 141, 589–597 (2010). https://doi.org/10.1007/s00706-010-0294-4

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  • DOI: https://doi.org/10.1007/s00706-010-0294-4

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