1. Academic Validation
  2. Antimalarial activity of novel 5-aryl-8-aminoquinoline derivatives

Antimalarial activity of novel 5-aryl-8-aminoquinoline derivatives

  • J Med Chem. 2011 Jan 13;54(1):131-42. doi: 10.1021/jm100911f.
Hiroaki Shiraki 1 Michael P Kozar Victor Melendez Thomas H Hudson Colin Ohrt Alan J Magill Ai J Lin
Affiliations

Affiliation

  • 1 Division of Experimental Therapeutics, Walter Reed Army Institute of Research, Silver Spring, Maryland 20910, United States.
Abstract

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 IC(50) 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.

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