Details

Autor(en) / Beteiligte

• Shiraki, Hiroaki
• Kozar, Michael P
• Melendez, Victor
• Hudson, Thomas H
• Ohrt, Colin
• Magill, Alan J
• Lin, Ai J

Titel

Antimalarial Activity of Novel 5-Aryl-8-Aminoquinoline Derivatives

Ist Teil von

• Journal of medicinal chemistry, 2011-01, Vol.54 (1), p.131-142

Ort / Verlag

United States: American Chemical Society

Erscheinungsjahr

2011

Quelle

MEDLINE

Beschreibungen/Notizen

• 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 derivatives 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 min, 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.