Improved HDAC Inhibition, Stronger Cytotoxic Effect and Higher Selectivity against Leukemias and Lymphomas of Novel, Tricyclic Vorinostat Analogues

Histone deacetylase (HDAC) inhibitors are a class of drugs used in the cancer treatment. Here, we developed library 19 analogues Vorinostat, an HDAC inhibitor lymphomas In replaced hydrophobic phenyl group with various tricyclic ‘caps’ possessing central, eight-membered, heterocyclic ring, and investigated activity cytotoxic effect on normal cell lines. We found that 3 out compounds, based dibenzo[b,f]azocin-6(5H)-one, 11,12-dihydrodibenzo[b,f]azocin-6(5H)-one, benzo[b]naphtho[2,3-f][1,5]diazocine-6,14(5H,13H)-dione scaffolds, showed better HDACs inhibition than referenced Vorinostat. leukemic line MV4-11 lymphoma Daudi, three compounds lower IC50 values These had higher selectivity against Daudi lines reference also observed strong correlation between effect. Cell derived from solid tumours: A549 (lung carcinoma) MCF-7 (breast adenocarcinoma) as well BALB/3T3 (normal murine fibroblasts) were less susceptible to tested. Developed derivatives show improved properties thus they could be considered possible agents for leukemia