Review
Anti-infective potential of natural products: How to develop a stronger in vitro ‘proof-of-concept’

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Abstract

Natural products, either as pure compounds or as standardized plant extracts, provide unlimited opportunities for new drug leads because of the unmatched availability of chemical diversity. To secure this, a number of pivotal quality standards need to be set at the level of extract processing and primary evaluation in pharmacological screening models. This review provides a number of recommendations that will help to define a more sound ‘proof-of-concept’ for antibacterial, antifungal, antiviral and antiparasitic potential in natural products. An integrated panel of pathogens is proposed for antimicrobial profiling, using accessible standard in vitro experimental procedures, endpoint parameters and efficacy criteria. Primary requirements include: (1) use of reference strains or fully characterized clinical isolates, (2) in vitro models on the whole organism and if possible cell-based, (3) evaluation of selectivity by parallel cytotoxicity testing and/or integrated profiling against unrelated micro-organisms, (4) adequately broad dose range, enabling dose–response curves, (5) stringent endpoint criteria with IC50-values generally below 100 μg/ml for extracts and below 25 μM for pure compounds, (6) proper preparation, storage and in-test processing of extracts, (7) inclusion of appropriate controls in each in vitro test replicate (blanks, infected and reference controls) and (8) follow-up of in vitro activity (‘hit’-status) in matching animal models (‘lead’-status).

Abbreviations

ATCC
American type culture collection
BSL
biosafety level
CFU
colony forming unit
CPE
cytopathic effect
EPTT
endpoint titration technique
EPS
extracellular polymeric substance
HMI
hirumi-9 medium
HSV
Herpes simplex virus
MBC
minimal bactericidal concentration
MH
Mueller-Hinton
MIC
minimal inhibitory concentration
MRSA
methicillin-resistant Staphylococcus aureus
NBT
nitro blue tetrazolium
NCCLS
national committee for clinical laboratory standards
PES
phenazine ethosulphate
SAB
Sabouraud
SI
selectivity index
TCID50
50% tissue culture infective dose
TSA
tryptic soy agar
TSB
tryptic soy broth
VRE
vancomycin-resistant Enterococci
WHO
World Health Organization

Keywords

Natural products
Antibacterial
Antifungal
Antiviral
Antiparasitic
Screening

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