Computer-Aided Molecular Design of a Histone Deacetylase (HDAC) Inhibitor, N-Hydroxy-N-Phenyloctanediamide (Vorinostat)

Vorinostat,(N-hydroxy-N-phenyloctanediamide) is in a class of medications called histone deacetylase (HDAC) inhibitors. It is a good chemotherapeutic agent for treating cutaneous T-cell lymphoma (CTCL, a type of cancer) in patients whose disease has not improved, has gotten worse, or has come back after taking other medications. Conformational analysis and geometry optimization of vorinostat was performed according to the Hartree-Fock (HF) calculation method by ArgusLab 4.0.1 software. Molecular mechanics calculations were based on specific interactions within the molecule. These interactions included stretching or compressing of bond beyond their equilibrium lengths and angles, torsional effects of twisting about single bonds, the Vander Waals attractions or repulsions of atoms that came close together, and the electrostatic interactions between partial charges in vorinostat due to polar bonds. The steric energy for vorinostat was calculated to be 0.030859 a.u. (19.364457 kcal/mol). It was concluded that the lowest energy and most stable conformation of vorinostat was 19.36445736 kcal/mol). The most energetically favourable conformation of vorinostat was found to have a heat of formation of 115441.244100 kcal/mol. The self-consistent field (SCF) energy was calculated by geometry convergence function using RHF/AM1 method in ArgusLab software. The most feasible position for vorinostat to act as histone deacetylase (HDAC) inhibitor was found to be -116.682947 au (-73219.720900 kcal/mol).