DFT and QSAR study of Catechol-O-methyltransferase (COMT) as inhibitors for Parkinson’s disease treatment

Abstract Parkinson’s disease is characterized by a lack of the neurotransmitter or cell-signaling molecule dopamine. Levodopa is a well-known drug for Parkinson’s disease since it induces dopamine. Catechol-O-methyltransferase (COMT) are enzymes that break down levodopa, limiting the amount delivered to the brain. COMT inhibitors act by extending the duration of action of levodopa, thus improving the amount of time benefit from levodopa. There are several FDA-approved COMT inhibitors used, such as Entacapone and Tolcapone. Tolcapone can penetrate blood-brain barrier (BBB), but most of the drug stays in the plasma because its high protein bound, and it has severe side effects, while Entacapone cannot penetrate BBB, which reduces drug efficiency. This study aims to design higher-efficiency drug inhibitors by investigating the physical properties in terms of total energy, total dipole moment and HOMO/LUMO band gap at DFT: B3LYP level using the LAN2DZ basis set, in addition to quantitative structure activity relationship (QSAR) calculations to test the biological activity of these drug inhibitors for the treatment of Parkinson’s disease.