Chemdraw professional 19

The Swiss Institute of Bioinformatics’ (SIB) free Swiss ADME online tool was employed to evaluate physicochemical properties and determine ADME descriptors, pharmacokinetic features, medicinal chemistry compatibility, and drug-like characteristics of the most powerful newly synthesised 7a, 7b, 7c, 7f, 8a, 8f, and 9e compounds. ChemDraw Professional 19.0 was used to draw the ligands, which were exported in SMILE format and then uploaded to an online server for evaluation.

The two-dimensional structures of itaconic acid, mesaconic acid and citraconic acid were sketched using ChemDraw professional 19.0 and were imported into the MOE window. The compounds were subjected to an energy minimization up to a gradient of 0.001 kcal mol⁻¹ Ų using the MMFF94x force field and R-field solvation model, then saved as an mdb file. The predominant protonation status of the compounds in aqueous medium at pH 7 was calculated via the compute | molecule | wash command in the database viewer window. X-Ray crystal structures of human SDHA in complex with the cofactor oxaloacetate (PDB ID: 6VAX)^{38 (link)}, porcine mitochondrial respiratory complex II, containing oxaloacetate (PDB ID: 3SFD)^{39 (link)}, human ACOD1 (PDB ID: 6R6U)^{2 (link)} and mouse ACOD1 (PDB ID: 6R6T)^{2 (link)} were used for the molecular docking studies. Potential was set up to Amber10:EHT as a force field and R-field for solvation. Addition of hydrogen atoms, removal of water molecules more than 4.5 Å from the ligand or receptor, correction of library errors and tethered energy minimization of the binding site were performed via the QuickPrep module.