N,N-Bis(trifluoromethylquinolin-4-yl)diamino alkanes: synthesis and antimalarial activity

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 chloroquine-resistant (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.