Methimazole and propylthiouracil design as a drug for anti-graves' disease: Structural studies, Hirshfeld surface analysis, DFT calculations, molecular docking, molecular dynamics simulations, and design as a drug for anti-graves' disease

• Published in: Journal of molecular structure Vol. 1289; p. 135913
• Main Authors: Edache, Emmanuel Israel, Uzairu, Adamu, Mamza, Paul Andrew, Shallangwa, Gideon Adamu, Azam, Mohammad, Min, Kim
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 05.10.2023
• Subjects: Docking; FT-IR; FT-Raman; Graves’ disease; Hirshfeld analysis; MD. Simulations; Methimazole; Propylthiouracil; Methimazole; Graves’ disease; FT-Raman; MD. Simulations; Hirshfeld analysis; Docking; FT-IR; Propylthiouracil
• ISSN: 0022-2860; 1872-8014
• DOI: 10.1016/j.molstruc.2023.135913

•Molecular structure of methimazole and propylthiouracil were studied using DFT Hirshfeld surface, and interactions energy analysis (IEA).•Fifteen new compounds were designed with improved docking scores, MM/GBSA analysis, and FT-IR vibrational assignments are performed on the basis on the PED via in-silico designing strategy on the optimized molecular structure.•The energetic motion and level of stability of the complexes were examined and understood using the MD simulation.•We anticipate that our approach may provide new avenues for optimizing and developing more potent Graves’ disease inhibitors. Methimazole (MMI) and propylthiouracil (PTU), two commonly used anti-Graves' disease drugs, were studied using density functional theory (DFT) with the B3LYP approach and 6–311G(d,p) as the basis set. Molecular electrostatic potential (MEP), Hirshfeld investigations, and interactions energy analysis (IEA) were used to study the surface of the compounds to identify the various reactive surfaces which are essential for determining a variety of biological activities. Using an in-silico designing technique, fifteen new compounds with enhanced activity and docking scores were developed on the basis of information acquired from the standard drugs (MMI and PTU). These novel compounds featured improved activity and docking score results. Furthermore, molecular dynamics simulations were carried out on the standard drugs as well as the compound D10 with the highest binding affinity using protein 5hpw. In addition to this, the NBOs, FT-IR, and FT-Raman spectra of D10, as well as some of its thermochemistry, were reported and examined. These findings may provide useful information for future development. [Display omitted]