Keynote Lecture 7 “From the discovery of bioactive natural products to the development of innovative strategies for their chemo-diversification and generation of potential new leads”

Over the past decade, we have witnessed a revolution in the methodologies applied to natural product research. Current approaches combine powerful metabolite profiling methods for compound annotation, and prioritization. Targeted isolation is performed using high-resolution chromatographic methods that closely match those used for analytical profiling. Thanks to these tools, minor bioactive compounds were identified. However, in plant extracts, the major compounds are generally common structures, apparently irrelevant for drug discovery. In this context, the chemical engineering of extracts and biotransformation could be an alternative to valorize them. The concept of these approaches is to start from abundant NPs present in plants to obtain active compounds using chemical and biological reactions. Given that 20% of marketed drugs contain halogen atoms, a methodology has been developed to allow controlled halogenation of compounds directly in plant extracts [1]. In addition, biotransformation reactions of single NPs using enzymes secreted by a phytopathogenic fungus have been successfully used to obtain a wide variety of compounds. A metabolite profiling by UHPLC-PDA-ELSD-HRMS analysis were used to monitor these different reactions and highlight the presence of the new compounds [2] [3] [4]. In most cases, it was possible to improve the chemical diversity by the generation of active compounds from inactive scaffolds. To isolate, characterize and study the biological activities of the generated compounds, the use of high- resolution preparative chromatographic methods was mandatory. At this level, significant improvements for the efficient targeted isolation of given NPs through dry load injection and chromatographic gradient transfer methods have been made [5]. The applications, possibilities and limitations of these latest technologies will be illustrated with recent investigations performed in our laboratory.

 

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Conflict of Interest

The authors declare no conflict of interest.

• References

• 1 Neuenschwander A, Rocha VPC, Bastos TM. et al. Production of highly active antiparasitic compounds from the controlled halogenation of the Arrabidaea brachypoda crude plant extract. J Nat Prod 2020; 83: 2631-2640
• 2 Huber R, Marcourt L, Koval A. et al. Chemoenzymatic synthesis of complex phenylpropanoid derivatives by the Botrytis cinerea secretome and evaluation of their wnt inhibition activity. Front Plant Sci 2021; 12: 805610
• 3 Huber R, Koval A, Marcourt L. et al. Chemoenzymatic synthesis of original stilbene dimers possessing wnt inhibition activity in triple-negative breast cancer cells using the enzymatic secretome of Botrytis cinerea Pers. Front Chem 2022; 10: 881298
• 4 Righi D, Huber R, Koval A. et al. Generation of stilbene antimicrobials against multiresistant strains of Staphylococcus aureus through biotransformation by the enzymatic secretome of Botrytis cinerea . J Nat Prod 2020; 83: 2347-2356
• 5 Queiroz EF, Alfattani A, Afzan A. et al. Utility of dry load injection for an efficient natural products isolation at the semi-preparative chromatographic scale. J Chromatogr A 2019; 1598: 85-91

Publikationsverlauf

Artikel online veröffentlicht:
16. November 2023