In this article, three series of 21, 4-aminoquinoline derivatives bearing a quinoline moiety (2a-b, 3a-c, and 4a-b) have been designed, synthesized, and evaluated as an antimalarial and antibacterial agent against the potent marketed drug. Compound (24)2c, (31)2i, 42(2o) and 32(3a) were found to be the most potent of all of the compounds tested, with an MIC value of 1μg/mL to 32μg/mL against several Gram-positive (Staphylococcus aureus 5345, Salmonella typhi 2501), Bacillus cereus 2217 and Gram-negative Escherichia coli 2931 strains of bacteria. In addition, compound 32(3a) showed potent inhibitory activity (MIC = 1μg/mL) against Salmonella typhi 2501, Bacillus cereus 2217 and Gram-negative Escherichia coli 2931 strains of bacteria indicating that its antibacterial spectrum is similar to those of the positive control ciprofloxacin. Structure-activity relationships (SAR) analyses and docking studies implicated the amino and amido side chain group formation responsible for in increasing the antimicrobial potency of the quinoline compounds. Five analogs were tested for inhibition of β-hematin formation as an antimalarial activities using standard chloroquine shows a good inhibition