Tukulula, M, Njoroge, M, Abay, ET, Mugumbate, GC, Wiesner, L, Taylor, D, Gibhard, L, Norman, J, Swart, KJ, Gut, J, Rosenthal, PJ, Barteau, S, Streckfuss, J, Kameni-Tcheudji, J and Chibale, K (2013) Synthesis and in Vitro and in Vivo Pharmacological Evaluation of New 4-Aminoquinoline-Based Compounds. ACS MEDICINAL CHEMISTRY LETTERS. pp. 1198-1202.

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

Item Type:	Article
Additional Information:	pubid: 210 nvp_institute: NIBR contributor_address: Univ Cape Town, Dept Chem, ZA-7701 Rondebosch, South Africa ; Univ Orange Free State, Dept Chem 48, Bloemfontein, South Africa, PAREXEL Int Clin Res Org, Bloemfontein, South Africa ; Univ Cape Town, Sch Med, Dept Pharmacol, ZA-7925 Observatory, South Africa ; PAREXEL Int Clin Res Org, Bloemfontein, South Africa ; Univ San Francisco, San Francisco Gen Hosp, Dept Med, San Francisco, CA 94143 USA ; Novartis Inst BioMed Res, CH-4057 Basel, Switzerland ; Univ Cape Town, Dept Chem, ZA-7701 Rondebosch, South Africa, Univ Cape Town, Inst Infect Dis & Mol Med, ZA-7701 Rondebosch, South Africa kelly.chibale@uct.ac.za; Univ Cape Town, Dept Chem, ZA-7701 Rondebosch, South Africa; Chibale, K; Univ Cape Town, Dept Chem, ZA-7701 Rondebosch, South Africa
Date Deposited:	13 Oct 2015 13:12
Last Modified:	13 Oct 2015 13:12
URI:	https://oak.novartis.com/id/eprint/22029