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Plant natural fragments, an innovative approach for drug discovery

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Abstract

Plant natural products (PNP) (e.g., secondary vegetal metabolites and their derivatives) have been a productive source of active ingredients for the pharmaceutical industry. The High Throughput Screening of Plant Natural Products (PNP-HTS) with extracts or isolated compounds has shown to be time consuming, expensive, and not as successful as expected. Recently building upon the innovative fragment-based drug discovery (FBDD) a disruptive approach was developed based on PNP. The fragment approach involves elaboration and/or isolation of weakly binding small molecules with molecular weights between 150 and 250 Da. This method is fundamentally different from HTS in almost every aspect (i.e., size of the compound library, screening methods, and optimization steps from hit to lead). Due to their nature, vegetal natural fragments have unique three-dimensional (3D) properties, high Fsp3, low aromaticity, and large chemo-diversities which represent potential opportunities for developing novel drugs. Preliminary results using vegetal natural fragments appear to be a promising and emerging field which offers valuable prospects for developing new drugs.

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Fig. 1
Fig. 2

From David and Ausseil (2014)

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Fig. 7

From Valenti et al. (2019)

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Fig. 10

Adapted from Cherry and Mitchell (2008), Scott et al. (2012)

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Abbreviations

ADMET:

Administration–distribution–metabolization–excretion–toxicology studies

FBDD:

Fragment based drug discovery

Fsp3 :

Ratio of sp3 carbon to the total number of carbon

HTS:

High throughput screening

MS:

Mass spectrometry

NMR:

Nuclear magnetic resonance

NP:

Natural products

PF:

Pierre Fabre

PFL:

Plant fragment library

PNP:

Plant natural products

SPR:

Surface plasmon resonance

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David, B., Grondin, A., Schambel, P. et al. Plant natural fragments, an innovative approach for drug discovery. Phytochem Rev 19, 1141–1156 (2020). https://doi.org/10.1007/s11101-019-09612-4

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