2. Academic Validation
  3. Novel nucleoside-based antimalarial compounds

Novel nucleoside-based antimalarial compounds

  • Bioorg Med Chem Lett. 2016 Jun 15;26(12):2861-2865. doi: 10.1016/j.bmcl.2016.04.053.
Zhaoyan Zheng 1,  Huu-Anh Tran 1,  Srinivasan Manivannan 1,  Xianghui Wen 1,  Marcel Kaiser 2,  Reto Brun 2,  Floyd F Snyder 3,  Thomas G Back 4
Affiliations

Affiliations

  • 1 Department of Chemistry, University of Calgary, 2500 University Drive NW, Calgary, Alberta T2N 1N4, Canada.
  • 2 Swiss Tropical and Public Health Institute, Socinstrasse 57, PO Box, 4002 Basel, Switzerland; University of Basel, 4003 Basel, Switzerland.
  • 3 Biochemical Genetics Lab, Alberta Children's Hospital, 2888 Shaganappi Trail NW, Calgary, Alberta T3B 6A9, Canada. Electronic address: [email protected].
  • 4 Department of Chemistry, University of Calgary, 2500 University Drive NW, Calgary, Alberta T2N 1N4, Canada. Electronic address: [email protected].
PMID: 27156774 DOI: 10.1016/j.bmcl.2016.04.053
Abstract

The malaria-causing parasite Plasmodium falciparum employs a salvage pathway for the biosynthesis of nucleotides, in contrast to de novo biosynthesis that is utilized by the human host. A series of twenty-two 2-, 6- and 5'-modified adenosine ribonucleosides was synthesized, with the expectation that these compounds would generate toxic metabolites instead of active nucleotides by the pathogen, while remaining inert in host cells. Bioassays with P. falciparum (K1 strain) indicated IC50 values as low as 110nM and a selectivity index with respect to cytotoxicity toward an L6 rat myoblast cell line of >1000 for the most potent analogue.

Keywords

Antimalarial compounds; Nucleosides; Purine salvage pathways.

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