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Piperazine-based dithiocarbamates serve as important scaffolds for numerous pharmacologically active drugs. The current study investigates the design and synthesis of a series of dithiocarbamates with a piperazine unit as well as their biological activities. Under ultrasound conditions, the corresponding piperazine-1-carbodithioates <b>5a</b>–<b>5j</b> were synthesized from monosubstituted piperazine <b>2</b> and <i>N</i>-phenylacetamides <b>4a</b>–<b>4j</b> in the presence of sodium acetate and carbon disulfide in methanol. The structures of the newly synthesized piperazines were confirmed, and their anti-lung carcinoma effects were evaluated. A cytotoxic assay was performed to assess the hemolytic and thrombolytic potential of the synthesized piperazines <b>5a</b>–<b>5j</b>. The types of substituents on the aryl ring were found to affect the anticancer activity of piperazines <b>5a</b>–<b>5j</b>. Piperazines containing 2-chlorophenyl (<b>5b</b>; cell viability = 25.11 ± 2.49) and 2,4-dimethylphenyl (<b>5i</b>; cell viability = 25.31 ± 3.62) moieties demonstrated the most potent antiproliferative activity. On the other hand, piperazines containing 3,4-dichlorophenyl (<b>5d</b>; 0.1%) and 3,4-dimethylphenyl (<b>5j</b>; 0.1%) rings demonstrated the least cytotoxicity. The piperazine with the 2,5-dimethoxyphenyl moiety (<b>5h</b>; 60.2%) showed the best thrombolytic effect. To determine the mode of binding, in silico modeling of the most potent piperazine (i.e., <b>5b</b>) was performed, and the results were in accordance with those of antiproliferation. It exhibits a similar binding affinity to PQ10 and an efficient conformational alignment with the lipophilic site of PDE10A conserved for PQ10A.