Antimalarial activity of n(6)-substituted adenosine derivatives (part 2).
We have investigated the in vitro antimalarial activity of a new series of adenosine derivatives. The results show that N(6)-(1-naphthylmethyl)-5'-deoxy-5'-(amido)adenosines as well as N(6)-(4-phenylbenzyl)-5'-deoxy-5'-(amido)adenosines display significant activity against the malaria-causing parasites, with the sterically demanding bisubstituted species reported being active in most cases in the low-micromolar range. The novel compounds with unusual substitution pattern were obtained applying an efficient convergent polymer-assisted solution-phase (cPASP) synthesis protocol. Thus, we were able to prepare a series of substituted derivatives in parallel that would have been difficult to synthesize by standard techniques. The scope and limitations of the synthetic methodology are discussed.
Herforth
Claudia
C
Institut für Pharmazie, Fachbereich Chemie, Universität Hamburg, Bundesstrasse 45, D-20146 Hamburg, Germany.
Wiesner
Jochen
J
Franke
Stephan
S
Golisade
Abolfasl
A
Jomaa
Hassan
H
Link
Andreas
A
D000241:Adenosine / Q000031:analogs & derivatives*; D000818:Animals; D000962:Antimalarials / Q000737:chemistry / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D010963:Plasmodium falciparum / Q000187:drug effects*; D016339:Spectrometry, Mass, Fast Atom Bombardment
D000962:Antimalarials; D000241:Adenosine