Some new 4-aminoquinoline derivatives were synthesized, characterized by their analytical and spectral data (IR, 1 HNMR, 13CNMR and MS), and screened for in vitro antimalarial activity against a chloroquine-sensitive strain of Plasmodium falciparum (3D7). Results clearly reveal that all the synthesized compounds possess in vitro antimalarial activity at the tested dose which, however, was considerably less than that of the standard reference drug, chloroquine. From results, it could be assumed that the presence of an aromatic bulky group with optimal lipophilicity at 1,3-thiazinan-4-one ring system might be an important requirement for the antimalarial activity of synthesized compounds, 6a–g. In addition to the evaluation of antimalarial activity, the synthesized compounds were also screened for antibacterial activity against six different strains of Gram-positive (Bacillus subtilis, Bacillus cereus, and Staphylococcus aureus) and Gram-negative bacteria (Escherichia coli, Pseudomonas aeruginosa, and Klebsiella pneumoniae). All the compounds at the tested doses were found to be active against all the tested organisms, but were less active as compared to the standard drug, ofloxacin. Results of antibacterial study indicate that aromatic bulky substituents have greater contributing effect than the aliphatic non-bulky group toward the antibacterial activity of the prepared 4-aminoquinoline derivatives.