Design, synthesis and in vitro antiplasmodial activity of some bisquinolines against chloroquine-resistant strain

A series of novel bisquinoline compounds comprising N¹ -(7-chloroquinolin-4-yl) ethane-1,2-diamine and 7-chloro-N-(2-(piperazin-1-yl)ethyl)quinolin-4-amine connected with 7-chloro-4-aminoquinoline containing various Amino acids is described. We have bio-evaluated the compounds against both chloroquine-sensitive (3D7) and chloroquine-resistant (K1) strains of Plasmodium falciparum in vitro. Among the series, compounds 4 and 7 exhibited 1.8- and 10.6-fold superior activity as compared to chloroquine (CQ; IC₅₀ = 0.255 ± 0.049 μm) against the K1 strain with IC₅₀ values 0.137 ± 0.014 and 0.026 ± 0.007 μm, respectively. Furthermore, compound 7 also displayed promising activity against the 3D7 strain (IC₅₀ = 0.024 ± 0.003 μm) of P. falciparum when compared to CQ. All the compounds in the series displayed resistance factor between 0.57 and 4.71 as against 51 for CQ. These results suggest that bisquinolines can be explored for further development as new antimalarial agents active against chloroquine-resistant P. falciparum.

Plasmodium falciparum; 4-Aminoquinoline; antiplasmodial activity; chloroquine; chloroquine-resistant strain; chloroquine-sensitive strain.