Searching for Drugs That Target Multiple Receptors for Anthelmintics from African Natural Products

Chapter

Abstract

Assay strategies that permit mechanism-based screening for new antiparasitic drugs on-site have been established at the Universities of Botswana and Cape Town. Researchers at these sites can take advantage of the chemical and biological diversity found in Africa to identify lead compounds for use against parasitic nematodes of local importance. The platform employs recombinant strains of yeast which express parasite proteins in a context that makes the survival of the microbe dependent on the function of the parasite drug target. African natural products can be subjected to high-throughput screening campaigns for discovery of compounds that selectively act on these parasite proteins. Yeast strains functionally expressing nematode G-protein-coupled receptors (GPCRs) allow detection of novel anthelmintic leads that interact with multiple receptors, reducing the chances of selecting drug-resistant parasite populations. Screening collections of African bio-extracts, to identify non-peptide ligands that target parasite GPCRs, provides local control of intellectual property rights, creating an economically sustainable platform. Revenues derived from agreements for leads for other indications of global economic value can fund further work to explore the chemistry embodied in the biodiversity of Africa to expand this platform beyond parasitic infections.

Keywords

Intellectual Property Drug Discovery Parasitic Nematode Chemical Space Antiparasitic Drug 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Abbreviations

ADME

Absorption, distribution, metabolism, and excretion

DMSO

Dimethyl sulfoxide

FLPs

FMRFamide-like peptides

FLP-GPCRs

FMRFamide-like peptide G-protein-coupled receptors

GPCR

G-protein-coupled receptor

HTS

High-throughput screening

IC50

Half maximal inhibitory concentration

IP

Intellectual property

MTA

Material transfer agreements

NTDs

Neglected tropical diseases

p450

Cytochrome p450

pANPL

pan-African Natural Product Library

R&D

Research and development

SAR

Structure–activity relationships

SOP

Standard operating procedure

TK

Traditional knowledge

UB

University of Botswana

UCT

University of Cape Town

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Copyright information

© Springer Berlin Heidelberg 2012

Authors and Affiliations

  1. 1.Institute of ParasitologyMcGill UniversitySte-Anne-de-BellevueCanada
  2. 2.Institute for the Study of International Development, Peterson HallMcGill UniversityMontrealCanada

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