Jump to main content
Jump to site search

Issue 3, 2017
Previous Article Next Article

Shining new light on ancient drugs: preparation and subcellular localisation of novel fluorescent analogues of Cinchona alkaloids in intraerythrocytic Plasmodium falciparum

Author affiliations

Abstract

Fluorescent derivatives of the archetypal antimalarial quinine and its diastereomer, quinidine, suitable for cellular imaging have been synthesised by attaching the small extrinsic fluorophore, NBD. Interactions of these derivatives with ferriprotoporphyrin IX were evaluated to verify that insights generated by live-cell imaging were relevant to the parent molecules. These analogues are shown by confocal and super-resolution microscopy to accumulate selectively in Plasmodium falciparum. Localisation to the region corresponding to the digestive vacuole supports the putative primary role of these alkaloids as haemozoin inhibitors. Quantitative analysis revealed minimal accumulation within the nucleus, rejecting the disruption of DNA replication as a possible mode of action. While extensive localisation to phospholipid structures and associated organelles was observed, the analogues did not show evidence of association with neutral lipid bodies.

Graphical abstract: Shining new light on ancient drugs: preparation and subcellular localisation of novel fluorescent analogues of Cinchona alkaloids in intraerythrocytic Plasmodium falciparum

Back to tab navigation

Supplementary files

Publication details

The article was received on 27 Sep 2016, accepted on 25 Oct 2016 and first published on 25 Oct 2016


Article type: Paper
DOI: 10.1039/C6OB02110G
Citation: Org. Biomol. Chem., 2017,15, 589-597
  •   Request permissions

    Shining new light on ancient drugs: preparation and subcellular localisation of novel fluorescent analogues of Cinchona alkaloids in intraerythrocytic Plasmodium falciparum

    J. G. Woodland, R. Hunter, P. J. Smith and T. J. Egan, Org. Biomol. Chem., 2017, 15, 589
    DOI: 10.1039/C6OB02110G

Search articles by author

Spotlight

Advertisements