Author:
Cowman, Alan F.,Deady, Leslie W.,Deharo, Eric,Desneves José,Tilley Leann
Abstract
A new type of bisquinoline antimalarial, containing the basic side chain of
the cinchona alkaloids, has been evaluated. Five bis ethers, from
10,11-dihydrocupreine linked through the 6′-hydroxy group by
-(CH2)2n- bridges
(n = 2-5) (series A), and six bis amides, from
8′-amino-10,11-dihydrocinchonidine linked by
-CO(CH2)2nCO- bridges
(n = 1-6) (series B), were synthesized and
screened against chloroquine-sensitive and -resistant strains and a
mefloquine-resistant strain of
Plasmodium falciparum in vitro. Two analogues of series
B (n= 4; 5), with a
2-(dibutylamino)-1-hydroxyethyl side chain (series C), were also included.
Compounds within series A were generally least active. Among the rest were
compounds as active as mefloquine, with diminished cross-resistance to the
mefloquine-resistant strain. The most potent (series B,
n = 4) was highly active against
chloroquine-sensitive, chloroquine-resistant and mefloquine-resistant
parasites. Invivo testing, however, showed the compound
to be too toxic for further development
Cited by
19 articles.
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