We report the synthesis of double, triple and quadruple extended side chain analogues of the antimalarial drug primaquine and some other 8-aminoquinolines. The synthesized analogues have exhibited potent antimalarial activities in vitro against both the drug-sensitive D6 strain (IC50 ¼ 0.19–0.92 mg mL-1 ) and the drug-resistant W2 strain (IC50 ¼ 0.12–0.82 mg mL-1 ) of P. falciparum and in vivo against drug-sensitive P. berghei infected mice (100% curative at 25 mg kg-1 day-1 , and resulted in either 4/6 or 5/6 cures at 10 mg kg-1 day-1 ) for the most promising structures. These analogues were also found to be free of cytotoxic effects at the highest test concentration of 23.8 mg mL-1 in a panel consisting of six cell lines. The promising 8-aminoquinolines inhibited b-hematin (IC50 ¼ 9.6–20.8 mM) in vitro underlining the disruption of the heme catabolism pathway in the malaria parasite as their potential biochemical pathway for antimalarial action. The analogues also displayed potent antileishmanial activities in vitro against L. donovani promastigotes (IC50 ¼ 1.6–32 mg mL-1 ; IC90 ¼ 4–40 mg mL-1 ) and moderate in vitro antimicrobial activities against a panel of bacteria and fungi.