Heteroaromatic derivatives (3a–f) have been synthesized and evaluated for their activity against four cancer cell lines. Among the studied compounds, 1-(7- Chloroquinolin-4-yl)-2-[(1H-pyrrol-2-yl)methylene]hydrazine (3e) exhibited an excellent cytotoxic activity against the referred lines, and especially on melanoma cells (MDAMB-435). In this case, compound 3e is four times more active than the standard substance Doxorubicin. Together with other results from our group, 7-chloro-4 quinolinylhydrazones derived from chloroquine could be considered a relevant finding toward the rational design of new leads for antitumor compounds.