Computer-aided drug design of an anti-angiogenic and immunomodulatory agent, -(2,4-dioxocyclohexyl)-1H-isoindole-1,3(2H)-dione (thalidomide)

Abstract

2-(2,4-dioxocyclohexyl)-1H-isoindole-1,3(2H)-dione (thalidomide) is an oral agent with anti-angiogenic and immunomodulatory properties. Computational geometry optimization was performed to determine the steric energy, heat of formation and self-consistent field(SCF) energy of thalidomide. The molecular mechanics potential energy function wer evaluated in terms of energies associated with bonded interactions (bond length, bond angle and dihedral angle) as well as non-bonded interactions (Vander Waals and electrostatic). Surfaces were created to visualize excited state properties such as highest occupied molecular orbital's, lowest unoccupied molecular orbital's and electrostatic potential (ESP) mapped density. Heat of Formation of thalidomide was 655.2578 kcal/mol, the steric energy calculated for thalidomide was 0.10063593 a.u. (63.150058kcal/mol) and SCF energy was found to be-119.890047 au (−75232.2088 00kcal/mol) as calculated by RHF/MNDO method using Arguslab 4.0.1 suite. The most feasible position for thalidomide to act as an anti-angiogenic and immunomodulatory agent, was found to be-119.890047 au (−75232.208800 kcal/mol)