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BACKGROUND AND OBJECTIVE Histone deacetylases (HDACs) are important therapeutic targets for many types of human cancers. A derivative of valproic acid, N-(2-hydroxyphenyl)-2-propylpentanamide (HO-AAVPA), has antiproliferative properties on some cancer cell lines and inhibits the HDAC1 isoform. MATERIALS AND METHODS In this work, HO-AAVPA was tested as an antiproliferative agent in U87-MG (human glioblastoma) and U-2 OS cells (human osteosarcoma), which are types of cancer that are difficult to treat, and its antiangiogenic properties were explored. RESULTS HO-AAVPA had antiproliferative effects at 48 h with an IC50 = 0.655 mM in U87-MG cells and an IC50 = 0.453 mM in U-2 OS cells. Additionally, in the colony formation assay, HO-AAVPA decreased the number of colonies by approximately 99% in both cell lines and induced apoptosis by 31.3% in the U-2 OS cell line and by 78.2% in the U87-MG cell line. Additionally, HO-AAVPA reduced the number of vessels in chorioallantoid membranes (CAMs) by approximately 67.74% and IL-6 levels in both cell lines suggesting that the biochemical mechanism on cancer cell of HO-AAVPA is different compared to VPA. CONCLUSION HO-AAVPA has antiproliferative effects on glioblastoma and osteosarcoma and antiangiogenic properties.