Molecular modelling studies of Histone Deacetylase inhibitors as anticancer agents

Background

Cancer causes death to over 7.6 million people every year. The disease can be classified as cells' uncontrolled division. This uncontrolled division of cells or uncontrolled growth is caused by DNA damage. This eventually results in genes mutations, which encodes cell division controlling proteins. Histone deacetylase (HDAC) is one among the principal targets for the anticancer drugs.

Methods

Molecular docking studies of nearly 60 Trichostatin A, SuberoylAnilide Hydroxamic Acid and Sulfonamide anilides which show good inhibitory activity against HDAC were carried out using GLIDE program of Schrödinger Suite 2009. Comparison of docking scores of the compounds with their respective QSAR IC₅₀ have also been made.

Results

From Trichostatin A and SuberoylAnilide Hydroxamic Acid analogues binding results, it was found that HDAC conformational changes are based on the ligand binding. C/N/O atoms present in the aliphatic chains of the analogues interacted well with the Zn²⁺ metal ion and active site amino acid residues to disrupt the enzymatic activity of target protein HDAC.

Conclusion

Analogue inhibition taken into study with the target protein HDAC assures to be an advantageous therapeutic approach in cancer treatment.