Abstract:
BACKGROUND : The altered expression of histone deacetylase family member
8 (HDAC8) has been found to be linked with various cancers, thereby making
its selective inhibition a potential strategy in cancer therapy. Recently,
plant secondary metabolites, particularly phenolic compounds, have been
shown to possess HDAC inhibitory activity. OBJECTIVE : In the present
work, we have evaluated the ability of cinnamaldehyde (CAL), cinnamic
acid (CA), and cinnamyl alcohol (CALC) (bioactives of Cinnamomum) as
well as aqueous cinnamon extract (ACE), to inhibit HDAC8 activity in vitro
and in silico. MATERIALS AND METHODS : HDAC8 inhibitory activity of ACE
and cinnamon bioactives was determined in vitro using HDAC8 inhibitor
screening kit. Trichostatin A (TSA), a well‑known anti‑cancer agent and HDAC
inhibitor, was used as a positive control. In silico studies included molecular
descriptor Analysis molecular docking absorption, distribution, metabolism,
excretion, and toxicity prediction, density function theory calculation and
synthetic accessibility program. RESULTS : Pharmacoinformatics studies
implicated that ACE and its Bioactives (CAL, CA, and CALC) exhibited
comparable activity with that of TSA. The highest occupied molecular
orbitals and lowest unoccupied molecular orbitals along with binding
energy of cinnamon bioactives were comparable with that of TSA.
Molecular docking results suggested that all the ligands maintained two
hydrogen bond interactions within the active site of HDAC8. Finally, the
synthetic accessibility values showed that cinnamon bioactives were easy
to synthesize compared to TSA. CONCLUSION : It was evident from both the
experimental and computational data that cinnamon bioactives exhibited
significant HDAC8 inhibitory activity, thereby suggesting their potential
therapeutic implications against cancer.
