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.
Kgokong
Joseph L
JL
Medicines Regulatory Affairs, National Department of Health, Private Bag X828, Pretoria. 0001. South Africa. kgokoj@health.gov.za
Matsabisa
Gilbert M
GM
Smithand
Peter P
PP
Breytenbach
Jaco C
JC
D000473:Alkanes / Q000138:chemical synthesis / Q000494:pharmacology*; D000634:Aminoquinolines / Q000138:chemical synthesis / Q000494:pharmacology*; D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis / Q000494:pharmacology*; D002738:Chloroquine / Q000494:pharmacology*; D004351:Drug Resistance; D006427:Hemin / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D008956:Models, Chemical; D021261:Parasitic Sensitivity Tests; D010879:Piperazines / Q000138:chemical synthesis / Q000494:pharmacology*; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000254:growth & development; D013056:Spectrophotometry, Ultraviolet / Q000379:methods; D013329:Structure-Activity Relationship
D000473:Alkanes; D000634:Aminoquinolines; D000962:Antimalarials; D010879:Piperazines; D006427:Hemin; D002738:Chloroquine