Planta Med 2016; 82(S 01): S1-S381
DOI: 10.1055/s-0036-1596131
Abstracts
Georg Thieme Verlag KG Stuttgart · New York

Phylogenetic relationships through the lens of chemoinformatic methods

A Henz
1   Division of Pharmacognosy, Department of Medicinal Chemistry, Uppsala University, BMC – Biomedical Center, Box 574, S-75123 Uppsala, Sweden
,
R Buonfiglio
2   Computational Chemistry, Chemistry Innovation Center, Discovery Science, AstraZeneca R&D Gothenburg, 43183 Mölndal, Sweden
,
T Kogej
2   Computational Chemistry, Chemistry Innovation Center, Discovery Science, AstraZeneca R&D Gothenburg, 43183 Mölndal, Sweden
,
A Backlund
1   Division of Pharmacognosy, Department of Medicinal Chemistry, Uppsala University, BMC – Biomedical Center, Box 574, S-75123 Uppsala, Sweden
› Author Affiliations
Further Information

Publication History

Publication Date:
14 December 2016 (online)

 

Natural Products (NPs) provide an enormous reservoir of chemical diversity and a corresponding diversity of biological activities. Amongst the approximate 350.000 species of higher plants only a fractional amount has been investigated phytochemically and pharmacologically [1]. To discover new drug leads from higher plants, the identification of a promising source plays a substantial role [2].

A long-standing hypothesis in phytochemistry states that among more advanced groups of angiosperms one would find more advanced chemistry.

In this study, the correspondence between phylogenetic relationships and chemical diversity is investigated in order to predict the chemical and possible pharmacological potential of a plant. For this purpose, a combination of phylogeny, chemography and chemoinformatic tools has been applied to analyse a comprehensive 'in-house' dataset of over 5.200 sesquiterpene lactones (STLs).

ChemGPS-NP, a tool to navigate chemical property space of Natural Products [3], was used to analyse the distribution of selected NPs in chemical space. Based on Principal Component Analysis (PCA), it allows an efficient analysis and comparison of compounds depending on their physico-chemical properties in multiple dimensions.

Through visualisation in the ChemGPS-NP global map, different volumes and trends mirroring how selected NPs evolve during evolution could easily be identified.

Changes in physico-chemical properties were calculated and similarities between compounds in chemical space were measured through the calculation of Euclidean Distances (ED). Further more, Extended-connectivity fingerprints (ECFPs) [4] were employed for cluster analysis as additional approach to investigate phylogenetic and chemical diversity.

Zoom Image

Here we show that a combination of phylogeny and in silico applications serve as a tool to predict the chemical potential of a plant. It enables a guided target selection, which eventually can be applied for a guided drug lead discovery.

Acknowledgments: The research leading to these results has received funding from the People Programme (Marie Curie Actions) of the European Union's Seventh Framework Programme FP7/2007 – 2013/under REA grant agreement n° 606895.

Keywords: Phylogeny, ChemGPS-NP, Chemoinformatics, Sesquiterpene Lactones.

References:

[1] Frabricant DS and Farnsworth NR. The value of plants used in traditional medicine for drug discovery. Environ Health Persp 2001; 109: 69 – 75

[2] Balunas MJ and Kinghorn AD. Drug discovery from medicinal plants. Life Sci 2005; 78: 431 – 441

[3] Larsson J, Gottfries J, Muresan S, Backlund A. ChemGPS-NP: Tuned for navigation in biologically relevant chemical space. J Nat Prod 2007; 70: 789 – 794

[4] Rogers D and Hahn M. Extended-connectivity fingerprints. J Chem Inf Comp Sci 2010; 50: 742 – 754