Synthesis, characterization, and vitro evaluation of new materials in vorinostat analogs containing biomolecules

Abstract

Histone deacetylase inhibitors are newly emerging chemotherapeutic agents which have shown great potential in the treatment of many types of cancers. Vorinostat (SAHA) is one of the FDA-approved histone deacetylase inhibitors as a chemotherapeutic agent. However, these agents have many drawbacks which may limit their clinical application such as low oral bioavailability, and low intracellular concentration in solid tumors which may require high doses leading to side and maybe toxic effects. In silico design, synthesis and characterization of new histone deacetylase inhibitors with biomolecules (biotin and phenylalanine) as a novel moiety were achieved successfully as analogs to vorinostat, hopefully, to overcome its limitations and increase the targetability. MTT assay of compounds 2c and 3d (which are biotin and phenylalanine-linked hydroxamate derivatives) showed higher antiproliferative activity than SAHA and 5-FU against MCF7 and lower cytotoxic effect against NHF cell lines which were consistent with the docking study results. These findings are encouraging for the involvement of biomolecules in the future development of histone deacetylase inhibitors.