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Synthesis and in vitro and in vivo pharmacological evaluation of new 4-aminoquinoline-based compounds.

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.

SUBMITTER: Tukulula M

PROVIDER: S-EPMC4027225 | biostudies-literature | 2013 Dec

REPOSITORIES: biostudies-literature

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Synthesis and in vitro and in vivo pharmacological evaluation of new 4-aminoquinoline-based compounds.

Tukulula Matshawandile M Njoroge Mathew M Abay Efrem T ET Mugumbate Grace C GC Wiesner Lubbe L Taylor Dale D Gibhard Liezl L Norman Jennifer J Swart Kenneth J KJ Gut Jiri J Rosenthal Philip J PJ Barteau Samuel S Streckfuss Judith J Kameni-Tcheudji Jacques J Chibale Kelly K

ACS medicinal chemistry letters 20131001 12

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 inhibit ...[more]

PMID: 24900630

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