N,N-Bis(trifluoromethylquinolin-4-yl)diamino Alkanes: Synthesis and Antimalarial Activity

Joseph   L.   Kgokong; Gilbert   M.   Matsabisa; Peter   P.   Smith; Jaco   C.   Breytenbach

doi:10.2174/157340608785700216

Abstract

A series of N,N-bis(trifluoromethylquinolin-4-yl)- and N,N-bis[2,8-bis(trifluoromethyl)quinolin-4-yl] diamino alkane and piperazine derivatives were synthesised by employing a simple and rapid displacement reaction of the 4-chloro group on the 2-trifluoromethyl- and 2,8-bis(trifluoromethyl)-quinoline by diaminoalkane or piperazine groups. Results of in vitro antimalarial activity evaluations of these compounds against the chloroquine-sensitive (D10) and chloroquineresistant (K1) strains of Plasmodium falciparum indicate that compounds with trifluoromethyl groups in both the 2 and 8 positions coupled with diaminoalkyl bridging chains of 2 to 6 carbon atoms exhibit a slightly higher activity than compound with only a trifluoromethyl group at position 2, and those with a piperazine bridge These compounds exhibit higher activity in the chloroquine-resistant than in the chloroquine-sensitive strains of the Plasmodium. Comparative studies indicate that the compounds are more selective in their cytotoxicity against the parasite cells. Except for compounds containing a piperazine bridge, this new series of compounds interact with ferriprotoporphyrin IX to more or less the same extent.

Keywords: N,N-Bis(Trifluoromethylquinolin-4-yl)diamino alkanes, N,N-bis[2,8-bis(trifluoromethyl)quinolin-4-yl]diamino alkanes, antimalarial activity, synthesis, Ferriprotoporphyrin IX, cytotoxicity

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