Design of Novel Drugs (P3TZ, H2P3TZ, M2P3TZ, H4P3TZ and M4P3TZ) Based on Zonisamide for Autism Treatment by Binding to Potassium Voltage-gated Channel Subfamily D Member 2 (Kv4.2)

Document Type: Research Paper

Authors

Synthesis and Molecular Simulation Laboratory, Chemistry Department, Pars Isotope Company, P.O. Box: 1437663181, Tehran, Iran

Abstract

The present research article relates to the discovery of the novel drugs based on Zonisamide to treatment of autism disease. In first step, the electronic properties, reactivity and stability of the said compound are discussed. To attain these properties, the said molecular structure is optimized using B3LYP/6-311++G(d,p) level of theory at room temperature. The frontier molecular orbitals (FMOs) energies are used to calculate the global reactivity indices. Based on these indices, Zonisamide is a high stable compound and has low reactivity. In the next step, the optimized molecular structure of Zonisamide is docked into the potassium voltage-gated channel subfamily D member 2 (Kv4.2) and ligand-receptor interactions are analyzed. After that, the novel molecular structures based on Zonisamide backbone are designed and optimized. Designing the novel drugs are done using changes the backbone of Zonisamide and various functional groups. The interactions of the optimized molecular structures with the said potassium channel are analyzed using docking study.Based on these studies, ten molecules showed better ligand-receptor binding than Zonisamide. Finally, the physicochemical properties of the title compounds are analyzed. The compounds P3TZ, H2P3TZ, M2P3TZ, H4P3TZ and M4P3TZ are our novel drugs to treatment of autism disease based on the molecular docking and physicochemical properties.

Keywords


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