Keynote Lecture 3 “Polypharmacology-correlated Molecular Networking and other Essential Bioactivity-correlating Techniques for Studying Desert-loving Eremophila spp. from Australia”

Eremophila is a genus of approximately 230 species endemic to Australia and mainly found in the arid regions of Western Australia. Eremophila spp. have been used for medicinal and cultural purposes by the Australian Aboriginal people, and Eremophila is rich in bioactive diterpenoids and sesquiterpenoids [1], [2]. The aim of this study was to apply omics and other state-of-the-art technologies for exploring the chemical and pharmacological properties of more than 300 plant samples collected in a large interdisciplinary project and use these data to select species for further drug lead discovery. For this purpose, we used molecular phylogenetics combined with computational metabolomics to pinpoint intraspecies relationships, high-resolution inhibition profiling as a bioactivity-correlating technique, and polypharmacology-labelled molecular networking for pinpointing metabolites correlated with multiple bioactivities. The results from these explorative studies enabled us to identify Eremophila species and/or individual metabolites correlated with (poly)pharmacological bioactivity – and extracts of these species were subsequent analysed by a combination of high-resolution inhibition profiling and hyphenated high-performance liquid chromatography, photodiode-array detection, solid-phase extraction, high-resolution mass spectrometry, and nuclear magnetic resonance spectroscopy, i.e., HR-inhibition inhibition profiling/HPLC-PDA-HRMS-SPE-NMR. This resulted in isolation of more than 120 new and structurally diverse serrulatane, cembrane, and viscidane diterpenoids [3], [4] as well as a new class of dimeric branched chain fatty acids formed by Diels Alder reactions [5]. Pharmacological activities included antibacterial, antihyperglycaemic, and cancer resistance-reversing properties. In conclusion, Eremophila is a rich source of structurally unique diterpenoids with multiple bioactivities, and thus continues to be an interesting genus for natural-products-based drug discovery.

 

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• References

• 1 Gericke O, Fowler RM, Heskes AM. et al. Navigating through chemical space and evolutionary time across the Australian continent in plant genus Eremophila. Plant J 2021; 108: 555-578
• 2 Wubshet SG, Tahtah Y, Heskes AM. et al. Identification of PTP1B and α-glucosidase inhibitory serrulatanes from Eremophila spp. by combined use of dual high-resolution PTP1B and α-glucosidase inhibition profiling and HPLC-HRMS-SPE-NMR. J Nat Prod 2016; 79: 1063-1072
• 3 Zhao Y, Kjærulff L, Kongstad KT. et al. 2(5H)-Furanosesquiterpenes from Eremophila bignoniiflora: High-resolution inhibition profiling and PTP1B inhibitory activity. Phytochemistry 2019; 166: 112054
• 4 Petersen MJ, Lund XL, Semple SJ. et al. Reversal of ABCG2/BCRP-mediated multidrug resistance by 5,3′,5′-trihydroxy-3,6,7,4′-tetramethoxyflavone isolated from the Australian desert plant Eremophila galeata. Biomolecules 2021; 11: 1534
• 5 Pedersen HA, Semple SJ, Buirchell B. et al. PTP1B-inhibiting branched-chain fatty acid dimers from Eremophila oppositifolia subsp. angustifolia identified by high-resolution PTP1B inhibition profiling and HPLC-PDA-HRMS-SPE-NMR analysis. J Nat Prod 2020; 83: 1598-1610

Publication History

Article published online:
12 December 2022