Synthesis of a series of N6-substituted adenosines with activity against trypanosomatid parasites.
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.
Link
Andreas
A
Institute of Pharmacy, Ernst-Moritz-Arndt-University, Friedrich-Ludwig-Jahn-Strasse 17, 17487 Greifswald, Germany. link@uni-greifswald.de
Heidler
Philipp
P
Kaiser
Marcel
M
Brun
Reto
R
D000241:Adenosine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology*; D000818:Animals; D020128:Inhibitory Concentration 50; D013329:Structure-Activity Relationship; D014344:Trypanocidal Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D016833:Trypanosoma brucei rhodesiense / Q000187:drug effects*; D014353:Trypanosomiasis, African / Q000188:drug therapy
D014344:Trypanocidal Agents; D000241:Adenosine