A newly synthesized small molecule: the evaluation against Alzheimer's Disease by in silico drug design and computational structure analysis methods

Şahin S., DEGE N.

JOURNAL OF MOLECULAR STRUCTURE, vol.1236, 2021 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Article
  • Volume: 1236
  • Publication Date: 2021
  • Doi Number: 10.1016/j.molstruc.2021.130337
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Chemical Abstracts Core, INSPEC
  • Keywords: Crystal structure analysis, Hirshfeld surface analysis, Alzheimer's disease, Tau protein, in silico, Molecular docking, CRYSTAL-STRUCTURE, FT-RAMAN, DISCOVERY, PHARMACOKINETICS, ABSORPTION, HYPOTHESIS, PIPERIDINE, PROTEINS, NMR
  • Ondokuz Mayıs University Affiliated: Yes


The submitted study reports the synthesis, crystal structure determination by the spectroscopic and non-spectroscopic methods, comparison of computational and experimental results, enclosure of the intermolecular interactions, comprehensive surface analysis by Hirshfeld method and electrostatic potential map, the examination of the electronic properties by Frontier Molecular Orbital (FMO) theory and Ultraviolet-Visible (UV-Vis) methods of an organic-structured molecule: (E)-1-(5-nitro-2-(piperidin1-yl)phenyl)-N-(m-tolyl) methanimine. Drug-likeness properties such as Lipinski's rule of five, Adsorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) have been investigated by in silico web based tools like SwissADME and ADMETlab. Besides the said, the determination studies of biological targets of the compound have also been carried out by in silico techniques. It has been found that the compound may be a substrate against both i) neurogenerative disease-related: microtubule-associated protein tau and ii) myotonic dystrophy-related: muscleblind like protein 1 targets. In this concept, the ligand's binding efficiency to the tau protein has been determined by in silico molecular docking tools such as AutoDock 4.2 and Molecular Graphics Laboratory (MGL) tools. The found results have shown that the compound is in harmony with Lipinski and others (Ghose, Veger, Egan, Muegge), which determine a compound's drug-likeness properties, with zero deviation. According to the results found by The Brain Or IntestinaL EstimateD (BOILED-Egg) permeation method, the compound is active in both gastrointestinal absorption and Blood-Brain Barrier (BBB) crossing. We have found the lowest binding energy value determined by molecular docking is-5.28 kcal/mol. The title compound can be an inhibitor against tau aggregation to combat neurodegenerative diseases. But it needs further studies to verify the predictions said via both advanced in silico methods and in vitro and in vivo studies.