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Structural similarities between some common fluorophores used in biology and marketed drugs, endogenous metabolites, and natural products

Steve O’Hagan, View ORCID ProfileDouglas B. Kell
doi: https://doi.org/10.1101/834325
Steve O’Hagan
1School of Chemistry, The University of Manchester, 131 Princess St, Manchester M1 7DN, UK
2Manchester Institute of Biotechnology, The University of Manchester, 131 Princess St, Manchester M 1 7DN, UK
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Douglas B. Kell
1School of Chemistry, The University of Manchester, 131 Princess St, Manchester M1 7DN, UK
2Manchester Institute of Biotechnology, The University of Manchester, 131 Princess St, Manchester M 1 7DN, UK
3Department of Biochemistry, Institute of Integrative Biology, Biosciences Building, University of Liverpool, Crown Street, Liverpool L69 7ZB, UK
4Novo Nordisk Foundation Centre for Biosustainability, Technical University of Denmark, Building 220, Kemitorvet, 2800 Kgs. Lyngby, Denmark
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  • ORCID record for Douglas B. Kell
  • For correspondence: dbk@liv.ac.uk
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ABSTRACT

Background It is known that at least some fluorophores can act as ‘surrogate’ substrates for solute carriers (SLCs) involved in pharmaceutical drug uptake, and this promiscuity is taken to reflect at least a certain structural similarity. As part of a comprehensive study seeking the ‘natural’ substrates of ‘orphan’ transporters that also serve to take up pharmaceutical drugs into cells, we have noted that many drugs bear structural similarities to natural products. A cursory inspection of common fluorophores indicates that they too are surprisingly ‘drug-like’, and they also enter at least some cells. Some are also known to be substrates of efflux transporters. Consequently, we sought to assess the structural similarity of common fluorophores to marketed drugs, endogenous mammalian metabolites, and natural products. We used a set of some 150 fluorophores.

Results The great majority of fluorophores tested exhibited significant similarity (Tanimoto similarity > 0.75) to at least one drug as judged via descriptor properties (especially their aromaticity, for identifiable reasons that we explain), by molecular fingerprints, by visual inspection, and via the “quantitative estimate of drug likeness” technique. It is concluded that this set of fluorophores does overlap a significant part of both drug space and natural products space. Consequently, fluorophores do indeed offer a much wider opportunity than had possibly been realised to be used as surrogate uptake molecules in the competitive or trans-stimulation assay of membrane transporter activities.

  • ABBREVIATIONS

    PCA
    Principal Components Analysis
    QED
    Quantitative Estimate of Drug-likeness
    QSAR
    Quantittaive Structure-Activity Relationship
    SLC
    solute carrier
    TS
    Tanimoto similarity
    UNPD
    Universal Natural Products Database
  • Copyright 
    The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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    Posted November 08, 2019.
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    Structural similarities between some common fluorophores used in biology and marketed drugs, endogenous metabolites, and natural products
    Steve O’Hagan, Douglas B. Kell
    bioRxiv 834325; doi: https://doi.org/10.1101/834325
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    Structural similarities between some common fluorophores used in biology and marketed drugs, endogenous metabolites, and natural products
    Steve O’Hagan, Douglas B. Kell
    bioRxiv 834325; doi: https://doi.org/10.1101/834325

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