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Coumarin-hydroxamic acid derivatives <b>7a</b>–<b>k</b> were herein designed with a dual purpose: as antiproliferative agents and fluorescent probes. The compounds were synthesized in moderate yields (30–87%) through a simple methodology, biological evaluation was carried out on prostate (PC3) and breast cancer (BT-474 and MDA-MB-231) cell lines to determine the effects on cell proliferation and gene expression. For compounds <b>7c</b>, <b>7e</b>, <b>7f</b>, <b>7i</b> and <b>7j</b> the inhibition of cancer cell proliferation was similar to that found with the reference compound at a comparable concentration (10 μM), in addition, their molecular docking studies performed on histone deacetylases 1, 6 and 8 showed strong binding to the respective active sites. In most cases, antiproliferative activity was accompanied by greater levels of cyclin-dependent kinase inhibitor p21, downregulation of the p53 tumor suppressor gene, and regulation of cyclin D1 gene expression. We conclude that compounds <b>7c</b>, <b>7e</b>, <b>7f</b>, <b>7i</b> and <b>7j</b> may be considered as potential anticancer agents, considering their antiproliferative properties, their effect on the regulation of the genes, as well as their capacity to dock to the active sites. The fluorescent properties of compound <b>7j</b> and <b>7k</b> suggest that they can provide further insight into the mechanism of action.