- Synthesis of Novel G Factor or Chloroquine-Artemisinin Hybrids and Conjugates with Potent Antiplasmodial Activity
-
A series of novel hybrids of artemisinin (ART) with either a phytormone endoperoxide G factor analogue (GMeP) or chloroquine (CQ) and conjugates of the same compounds with the polyamines (PAs), spermidine (Spd), and homospermidine (Hsd) were synthesized and their antiplasmodial activity was evaluated using the CQ-resistant P. falciparum FcB1/Colombia strain. The ART-GMeP hybrid 5 and compounds 9 and 10 which are conjugates of Spd and Hsd with two molecules of ART and one molecule of GMeP, were the most potent with IC50 values of 2.6, 8.4, and 10.6 nM, respectively. The same compounds also presented the highest selectivity indexes against the primary human fibroblast cell line AB943 ranging from 16 372 for the hybrid 5 to 983 for the conjugate 10 of Hsd.
- Athanassopoulos, Constantinos M.,Baltas, Michel,Grellier, Philippe,Menendez, Christophe,Mouray, Elisabeth,Papaioannou, Dionissios,Pepe, Dionissia A.,Toumpa, Dimitra,André-Barrès, Christiane
-
-
Read Online
- Xylylated dimers of putrescine and polyamines: Influence of the polyamine backbone on spermidine transport inhibition
-
Dimeric norspermidine and spermidine derivatives are strong competitive inhibitors of polyamine transport. A xylyl tether was used for the dimerization of various triamines and spermine via a secondary amino group, and of putrescine via an ether or an amino group. Dimerization of putrescine moieties potentiates their ability to compete against spermidine transport to a much greater extent than for triamine dimers.
- Covassin, Laurence,Desjardins, Michel,Soulet, Denis,Charest-Gaudreault, Rene,Audette, Marie,Poulin, Richard
-
p. 3267 - 3271
(2007/10/03)
-