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A novel class of hybrid 4-anilinoquinoline triazines have been synthesized and evaluated in vitro for their antimalarial activity against CQ-sensitive 3D7 strain of P. falciparum as well as for their cytotoxicity toward VERO cell line. Five compounds (19, 20, 23, 41 and 45) exhibited the antimalarial potency superior to CQ. Compounds 14 and 16 were found to be orally active at a dose of 100 mg/kg×4 days against CQ-resistant strain of P. yoelii. Inhibition of β-hematin formation assay and molecular docking study has been conducted in order to gain insight into the mechanism of action of proposed targets for the 4-anilinoquinoline and triazine moiety of the hybrid compounds., (Copyright © 2010 Elsevier Masson SAS. All rights reserved.)

Despite emergence of resistance to CQ and other 4-aminoquinoline drugs in most of the endemic regions, research findings provide considerable support that there is still significant potential to discover new affordable, safe, and efficacious 4-aminoquinoline antimalarials. In present study, new side chain modified 4-aminoquinoline derivatives and quinoline-acridine hybrids were synthesized and evaluated in vitro against NF 54 strain of Plasmodium falciparum. Among the evaluated compounds, compound 17 (MIC=0.125 μg/mL) was equipotent to standard drug CQ (MIC=0.125 μg/mL) and compound 21 (MIC=0.031 μg/mL) was four times more potent than CQ. Compound 17 showed the curative response to all the treated swiss mice infected with CQ-resistant N-67 strain of Plasmodium yoelii at the doses 50 mg/kg and 25 mg/kg for four days by intraperitoneal route and was found to be orally active at the dose of 100 mg/kg for four days. The promising antimalarial potency of compound 17 highlights the significance of exploring the privileged 4-aminoquinoline class for new antimalarials., (Copyright © 2010. Published by Elsevier Ltd.)