O'Hagan, Steve and Kell, Douglas B 
ORCID: 0000-0001-5838-7963
(2020)
Structural Similarities between Some Common Fluorophores Used in Biology, Marketed Drugs, Endogenous Metabolites, and Natural Products.
MARINE DRUGS, 18 (11).
E582-.
Abstract
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 along with standard fingerprinting methods and the Tanimoto similarity metric. 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 with a significant part of both the 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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | drugs, natural products, fluorophores, fingerprinting, similarity, cheminformatics, rdkit, Tanimoto distance |
| Divisions: | Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 12 Jul 2021 09:46 |
| Last Modified: | 10 Feb 2024 03:12 |
| DOI: | 10.3390/md18110582 |
| Open Access URL: | https://doi.org/10.3390/md18110582 |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3129721 |
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