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Plant natural fragments, an innovative approach for drug discovery

  • Bruno DavidEmail author
  • Antonio Grondin
  • Philippe Schambel
  • Marc Vitorino
  • Denis Zeyer
Article
  • 206 Downloads

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.

Keywords

Fragment Drug discovery Fragment-based drug discovery Ligand efficiency 

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

Notes

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© Springer Nature B.V. 2019

Authors and Affiliations

  1. 1.Pôles Actifs Végétaux et ChemoinformatiqueInstitut de Recherche Pierre FabreToulouseFrance
  2. 2.NovAliXIllkirchFrance

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