Journal
JOURNAL OF MEDICINAL CHEMISTRY
Volume 54, Issue 1, Pages 131-142Publisher
AMER CHEMICAL SOC
DOI: 10.1021/jm100911f
Keywords
-
Categories
Funding
- Walter Reed Army Institute of Research
Ask authors/readers for more resources
In an attempt to separate the antimalarial activity of tafenoquine (3) from its hemolytic side effects in glucose-6-phosphate dehydrogenase (G6PD) deficiency patients, a series of 5-aryl-8-aminoquinoline derivative, was prepared and assessed for antimalarial activities The new compounds were found metabolically stable in human and mouse microsomal preparations, with t(1/2) > 60 mm, and were equal to or more potent than primaquine (2) and 3 against Plasmodium falciparum cell growth The new agents were more active against the chloroquine (CQ) resistant clone than to the CQ-sensitive clone Analogues with electron donating groups showed better activity than those with electron withdrawing substituents Compounds 4bc, 4bd, and 4be showed comparable therapeutic index (TI) to that of 2 and 3, with TI ranging from 5 to 8 based on IC50 data The new compounds showed no significant causal prophylactic activity in mice infected with Plasmodium berghei sporozoites, but are substantially less toxic than 2 and 3 in mouse tests
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available