Abstract |
A new class of 4-aminoquinolines was synthesized and evaluated in vitro for antiplasmodial activity against both the chloroquine-sensitive (3D7) and -resistant (K1 and W2) strains. The most active compounds 3c-3e had acceptable cytotoxicity but showed strong inhibition toward a panel of cytochrome P450 enzymes in vitro. Pharmacokinetic studies on 3d and 3e in mice showed that they had moderate half-life (4-6 h) and low oral bioavailability. The front runner compound 3d exhibited moderate inhibition of the malaria parasite on P. berghei infected mice following oral administration (5 mg/kg), achieving reduction of parasitemia population by 47% on day 7.
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Authors | Matshawandile Tukulula, Mathew Njoroge, Efrem T Abay, Grace C Mugumbate, Lubbe Wiesner, Dale Taylor, Liezl Gibhard, Jennifer Norman, Kenneth J Swart, Jiri Gut, Philip J Rosenthal, Samuel Barteau, Judith Streckfuss, Jacques Kameni-Tcheudji, Kelly Chibale |
Journal | ACS medicinal chemistry letters
(ACS Med Chem Lett)
Vol. 4
Issue 12
Pg. 1198-202
(Dec 12 2013)
ISSN: 1948-5875 [Print] United States |
PMID | 24900630
(Publication Type: Journal Article)
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