Pyrazolo [3,4-d]pyrimidine-based dual HDAC/Topo II inhibitors: Design, synthesis, and biological evaluation as potential antitumor agents.

• A series of pyrazolo [3,4- d ]pyrimidine-based dual HDAC/Topo II inhibitors were synthesized and evaluated for their anticancer activity. • Most of them showed exhibited excellent inhibitory activity against HDAC and selective inhibition for Topoisomerase II. Compounds 10f, 12, 22e, 22f and 22g showed excellent inhibitory activities against HDAC and Topo II. • Most of them showed potential anticancer activity in vitro. • Compounds 12 and 24 could promote apoptosis in MCF-7 cells. A series of pyrazolo [3,4- d ]pyrimidine-based dual HDAC/Topo II inhibitors were designed and synthesized by the pharmacophore fusion strategy. Their inhibitory activities towards HDAC and Topo and their cytotoxicity in cancer cell lines were evaluated. Among all of the synthesized compounds, 10f, 12, 22e, 22f , and 22g showed excellent dual inhibitory activities against HDAC and Topo II. MTT assays indicated that all the compounds displayed potent activity and compounds 10g, 12, 16b , and 24 which IC 50 value was 4.22 μM, 3.57 μM, 4.82 μM and 4.61 μM respectively significantly inhibited the migration of MCF-7 cells. Further studies revealed that compounds 12 and 24 could promote apoptosis in MCF-7 cells. Molecular docking studies revealed significant interaction of compounds 12 and 24 with active sites of HDAC and Topo II. [ABSTRACT FROM AUTHOR]