English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Background  A diverse library of pre-fractionated plant extracts, generated by an automated high-throughput system, was tested using an in vitro anti-malarial screening platform to identify known or new natural products for lead development. The platform identifies hits on the basis of in vitro growth inhibition of  Plasmodium falciparum  and counter-screens for cytotoxicity to human foreskin fibroblast or embryonic kidney cell lines. The physical library was supplemented by early-stage collection of analytical data for each fraction to aid rapid identification of the active components within each screening hit.    Results  A total of 16,177 fractions from 1300 plants were screened, identifying several  P. falciparum  inhibitory fractions from 35 plants. Although individual fractions were screened for bioactivity to ensure adequate signal in the analytical characterizations, fractions containing less than 2.0 mg of dry weight were combined to produce combined fractions (COMBIs). Fractions of active COMBIs had EC 50  values of 0.21–50.28 and 0.08–20.04 µg/mL against chloroquine-sensitive and -resistant strains, respectively. In  Berberis thunbergii , eight known alkaloids were dereplicated quickly from its COMBIs, but berberine was the most-active constituent against  P. falciparum . The triterpenoids  α -betulinic acid and  β -betulinic acid of  Eugenia rigida  were also isolated as hits. Validation of the anti-malarial discovery platform was confirmed by these scaled isolations from  B. thunbergii  and  E. rigida .    Conclusions  These results demonstrate the value of curating and exploring a library of natural products for small molecule drug discovery. Attention given to the diversity of plant species represented in the library, focus on practical analytical data collection, and the use of counter-screens all facilitate the identification of anti-malarial compounds for lead development or new tools for chemical biology.    Electronic supplementary material  The online version of this article (doi:10.1186/s12936-016-1313-7) contains supplementary material, which is available to authorized users.

Diversity-oriented natural product platform identifies plant constituents targeting Plasmodium falciparum