1207535-46-3Relevant academic research and scientific papers
Quinoline antimalarials containing a dibemethin group are active against chloroquinone-resistant plasmodium falciparum and inhibit chloroquine transport via the P. falciparum chloroquine-resistance transporter (PfCRT)
Zishiri, Vincent K.,Joshi, Mukesh C.,Hunter, Roger,Chibale, Kelly,Smith, Peter J.,Summers, Robert L.,Martin, Rowena E.,Egan, Timothy J.
, p. 6956 - 6968 (2011)
A series of 4-amino-7-chloroquinolines with dibenzylmethylamine (dibemethin) side chains were shown to inhibit synthetic hemozoin formation. These compounds were equally active against cultures of chloroquine-sensitive (D10) and chloroquine-resistant (K1) Plasmodium falciparum. The most active compound had an IC50 value comparable to that of chloroquine, and its potency was undiminished when tested in three additional chloroquine-resistant strains. The three most active compounds exhibited little or no cytotoxicity in a mammalian cell line. When tested in vivo against mouse malaria via oral administration, two of the dibemethin derivatives reduced parasitemia by over 99%, with mice treated at 100 mg/kg surviving the full length of the experiment. Three of the compounds were also shown to inhibit chloroquine transport via the parasite's chloroquine-resistance transporter (PfCRT) in a Xenopus oocyte expression system. This constitutes the first example of a dual-function antimalarial for which the ability to inhibit both hemozoin formation and PfCRT has been demonstrated directly.
QUINOLINE COMPOUNDS CONTAINING A DIBEMETHIN GROUP
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Page/Page column 38-39, (2010/04/03)
4-Amino-7-chloroquinolines are described containing dibenzylmethylamine (dibemethin) side chains attached via a methylene bridge to the amino group of the quinoline showing strong antimalarial and resistance reversing activity. The compounds are of the general formula (I), wherein X1, X2, X3 and X4 are independently selected from the group consisting of H, alkoxy, amido, optionally substituted amino, cyano, halo, haloalkyl, hydroxyl, nitro, sulphonamide and trifluoromethyl; Y is CH or N; m, n, p, q, r and s are independently from 0 to 5; R1, R2, R3 and R4 are independently selected from the group consisting of H, optionally substituted alkyl, alkenyl, alkynyl cycloalkyl, aryl, heteroaryl and heterocyclyl, wherein R3 and R4 together with the carbon atoms to which they are joined optionally form a six membered ring; or pharmaceutically acceptable salts thereof. Pharmaceutical compositions containing at least one of these compounds are also described for treating or preventing malaria.
