Synthesis of a series of N6-substituted adenosines with activity against trypanosomatid parasites.

Abstract

The involvement of purine salvage in the accumulation of current trypanocidal drugs is important for the treatment of African sleeping sickness. The substrate specificity of essential nucleoside transporters is therefore of physiological and pharmacological interest. With the intention to contribute to the knowledge in the field, a series of 16 adenosine derivatives with substituents in N(6)-position were prepared in order to evaluate their potential to inhibit Trypanosoma brucei spp. in vitro. An unmodified ribose moiety was selected to conserve key molecular recognition motifs of the arsenal of integral membrane proteins expressed in large numbers on the protozoan plasma membrane. Two of the new compounds prepared using a polymer-assisted acylation protocol showed antitrypanosomal activities in the single digit micromolar concentration range.

• Authors: Andreas Link, Philipp Heidler, Marcel Kaiser, Reto Brun
• Journal: European journal of medicinal chemistry (Eur J Med Chem) Vol. 44 Issue 9 Pg. 3665-71 (Sep 2009) ISSN: 1768-3254 [Electronic] France
• PMID: 19285758 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Trypanocidal Agents
• Adenosine

Topics

• Adenosine (analogs & derivatives, chemical synthesis, pharmacology)
• Animals
• Inhibitory Concentration 50
• Structure-Activity Relationship
• Trypanocidal Agents (chemical synthesis, chemistry, pharmacology)
• Trypanosoma brucei rhodesiense (drug effects)
• Trypanosomiasis, African (drug therapy)