Synthesis and anti-trypanosomal activity of various 8-aza-7-deaza-5'noraristeromycin derivatives.
A recent observation that (+)-7-deaza-5'-noraristeromycin (1), as an L-like analogue of aristeromycin, possessed meaningful anti-trypanosomal properties has prompted a search of other 7-deazapurines with similar or improved anti-trypanosomal responses. In that direction a series of pyrazolo[3,4-d]pyrimidines (that is, 8-aza-7-deaza-5'-noraristeromycin derivatives, 2-11) related to 1 have been prepared. These derivatives were evaluated against bloodstream forms of Trypanosoma brucei brucei and Trypanosoma brucei rhodesiense grown in vitro. Of these compounds, the parent L-like derivative 2 was less potent (IC50 40-70 microM) than 1 (IC50 0.165-5.3 microM) whereas the D-like analogue 3 was inactive, which is the same trend observed previously with 7-deaza-5'-noraristeromycin. Interestingly, some moderate activity (IC50 12.2-16.8 microM) was seen in the D-like 4'-methyl derivative 7 while its L-like partner was inactive.
Seley
K L
KL
Department of Chemistry, Auburn University, Alabama 36849-5312, USA.
Schneller
S W
SW
Rattendi
D
D
Lane
S
S
Bacchi
C J
CJ
D000241:Adenosine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D002522:Chlorocebus aethiops; D006367:HeLa Cells; D006801:Humans; D008956:Models, Chemical; D014344:Trypanocidal Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D014709:Vero Cells
C092763:7-deaza-5'-noraristeromycin; D014344:Trypanocidal Agents; D000241:Adenosine