Molecular Diversity

, Volume 14, Issue 2, pp 215–224 | Cite as

Parallel synthesis of a series of non-functional ATP/NAD analogs with activity against trypanosomatid parasites

  • Andreas Link
  • Philipp Heidler
  • Marcel Kaiser
  • Reto Brun
Full-Length Paper

Abstract

Non-functional analogs of the cofactors ATP and NAD are putative inhibitors of ATP- or NAD-dependant enzymes. Since pathogenic protozoa rely heavily on the salvage of purine nucleosides from the bloodstream of their host, such compounds are of interest as antiplasmodial and antitrypanosomal agents with a multitude of molecular targets. By replacing the negatively charged phosphate residues with a constrained unsaturated amide spacer and the nicotinamide moiety of NAD with various lipophilic substituents, 15 new ATP/NAD analogs were obtained in screening quantities. In these compounds, a 5′-desoxyadenosine moiety was conserved as key molecular recognition motif. The inhibition of P. falciparum and T. brucei ssp. in a whole parasite in vitro assay is reported.

Keywords

Adenosine ATP NAD Trypanosomes Polymer-bound reagents 

Abbreviations

BAD

Benzamide adenine dinucleotide

CDK

Cyclin-dependent kinase

COMT

Catechol O-methyltransferase

DIC

N,N′-Diisopropyl-carbodiimide

DMAP

4-Dimethylamino-pyridine

DMF

N,N-Dimethyl formamide

GAPDH

Glyceraldehyde phosphate dehydrogenase

HOBt

N-Hydroxy benzotriazole

MPLC

Medium pressure liquid chromatography

NEK

(Never-in-mitosis-A)-related protein kinase

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Copyright information

© Springer Science+Business Media B.V. 2009

Authors and Affiliations

  • Andreas Link
    • 1
  • Philipp Heidler
    • 2
  • Marcel Kaiser
    • 3
  • Reto Brun
    • 3
  1. 1.Institute of PharmacyErnst-Moritz-Arndt-UniversityGreifswaldGermany
  2. 2.Institute of Pharmaceutical ChemistryPhilipps-University MarburgMarburgGermany
  3. 3.Swiss Tropical InstituteBaselSwitzerland

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