Quinoline-isoniazid-phthalimide triads have been synthesised to assess their antiplasmodial efficacy and cytotoxicity against chloroquine-resistant W2 strain of P. falciparum and Vero cells, respectively. Most of the synthesized compounds displayed IC<sub>50</sub> in lower nM range and appeared to be approximately five to twelve fold more active than chloroquine. Heme-binding studies were also carried out to delineate the mode of action. The promising compounds with IC<sub>50s</sub> in range of 11-30 nM and selectivity index >2800, may act as promising template for the design of new antiplasmodials.