Evaluation of Medicinal Effects of Isoxazole Ring Isosteres on Zonisamide for Autism Treatment by Binding to Potassium Voltage-Gated Channel Subfamily D Member 2 (Kv 4.2)

Abstract

The present research study discusses discovery of the novel drugs based on Zonisamide (FDA-approved drug) to treat the autism disease. We designed novel compounds by changing the pyrazole ring of the molecular structure with its isosteric rings. The main goal of the present study is evaluation of isosterism effect on Zonisamide compound. The studied pyrazole isosters are isothiazole, [c] azaphosphole, [d] azaphosphole, oxaphosphole, thiaphosphole and diphosphole. First, all designed molecular structures were optimized using density functional theory (DFT) computational method by B3LYP/6-311++G(d,p) basis set of theory. All the computations were performed in isolated form at room temperature. Then, making complex of all optimized molecular structures with A-type potassium voltage gated subfamily d member 2 (Kv 4.2) was studied. The ligand-receptor complexes energy data showed all designed molecules except (1H-indazol-3-yl)methanesulfonamide interct with channel weakly. The residues Phe 75, Asp 86, Phe 84, and Phe 74 played main role in making complex with (1H-indazol-3-yl)methanesulfonamide. However, the ADME and biological properties of the designed molecules were carried out using swissADME and FAF-Drugs4 web tools. Based on the ligand-channel complexes docking data and biochemical properties of the compounds, the pyrazole pentet ring is a suitable isostere for isoxazole ring in Zonisamide.

Withaferin A (WIT) Interaction with beta–Tubulin to Promote Tubulin Degradation: In Silico Study

“…Its stability, reactivity and electronic properties were investigated via calculating the global reactivity indices. The frontier molecular orbitals (FMOs) energies were used to compute the titled indices [28][29][30][31]. In the next step, the optimized molecular structure was embedded into the active site of the protein.…”

“…Calculating the global reactivity indices is a good way to study the stability and reactivity properties of a chemical compound [28][29][30][31][32].The global reactivity descriptors like energy gap (Eg), ionization potential (IP), electron affinity (EA), chemical hardness (η), chemical softness (S), electronegativity (χ), electronic chemical potential (µ) and electrophilicity index (ω) can be obtained from the energies of the frontier orbitals. These reactivity indices are achieved by following formulas [33]: Fig.…”

Eccentric connectivity indices of titania nanotubes TiO2[m;n]

“…A basic concept of chemistry is that the properties/activities of a molecule depend upon its structural characteristics. Molecular graphs can be used to model the chemical structures of molecules and molecular compounds, by considering atoms as vertices and the chemical bonds between the atoms as edges [1][2][3]. In the study of quantitative structure-property and structure-activity relationships (QSPR/QSAR), the topological indices are very helpful in detecting the biological activities of a chemical compound [4][5][6][7].…”

On ve-degree atom-bond connectivity, sum-connectivity, geometric-arithmetic and harmonic indices of copper oxide

“…Graph theory has many applications in chemical and physical sciences. Graphs enable to model molecules and compounds as chemical graphs [1][2][3]. A topological index is a closed formula derived from chemical graphs.…”