Anti-malarial activity of N(6)-substituted adenosine derivatives. Part I.
The synthesis and biological evaluation of novel N(6)-substituted adenosine derivatives is reported. The first series of compounds was obtained using an established procedure for the nucleophilic substitution of a 1-(6-chloro-purin-9-yl)-beta-D-1-deoxy-ribofuranose with various amines. In addition, attachment of two different amino-functionalised spacer arms at the N(6)-position of adenosine enabled derivatisation by an innovative polymer-assisted protocol. Thus, we were able to prepare three series of substituted derivatives that displayed activity versus the multiresistant Plasmodium falciparum strain Dd2 in cell culture experiments.
Golisade
Abolfasl
A
Institut für Pharmazie, Universität Hamburg, Bundesstrasse 45, D-20146 Hamburg, Germany.
Wiesner
Jochen
J
Herforth
Claudia
C
Jomaa
Hassan
H
Link
Andreas
A
D000241:Adenosine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D000588:Amines / Q000737:chemistry; D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D020650:Combinatorial Chemistry Techniques / Q000379:methods; D004912:Erythrocytes / Q000382:microbiology; D006801:Humans; D020128:Inhibitory Concentration 50; D010963:Plasmodium falciparum / Q000187:drug effects / Q000254:growth & development
D000588:Amines; D000962:Antimalarials; D000241:Adenosine