rt Synthesis of 3-methyl-N-((4′-(3-methylbenzamido)-[1,1′-biphenyl]-4-yl)carbamothioyl)benzamide, X-ray structural analysis, DFT-guided investigation, Hirshfeld analysis and docking to jack bean urease

• Published in: Journal of molecular structure 2024-09, Vol.1311, p.138399, Article 138399
• Main Authors: Younas, Faiza, Saeed, Aamer, Hökelek, Tuncer, Schulzke, Carola, Tahira, Sarwat, Elvers, Benedict J., Saeed, Muhammad
• Format: Article
• Language: English
• Subjects: Acyl thiourea; Amide group; Benzidine; DFT studies, molecular docking; Hirshfeld analysis; Jack been urease inhibition; X-Ray diffraction structural analysis
• ISSN: 0022-2860; 1872-8014
• DOI: 10.1016/j.molstruc.2024.138399

•A novel compound comprising an acyl-thiourea and amide functional in a single molecular architecture (VII) was successfully prepared in high yield.•SC-XRD, Molecular Docking (MD) study against jack bean urease enzyme, DFT and Hirshfeld analyses were carried out.•Electrostatic interactions, dispersion effects, and total energy components proposes that the primary factor driving crystal stabilization is the electrostatic energy contribution.•The MD studies reveal notable H-bonding, CH π interactions with the active site of urease signifying a potent inhibitor. The new compound 3-methyl-N-((4′-(3-methylbenzamido)-[1,1′-biphenyl]-4-yl)carbamothioyl) benzamide (VII) was prepared with a room temperature procedure. It was synthesized in situ in three steps with an excellent yield of 85 %. The chemical structure of VII was confirmed spectroscopically. Its molecular structure was determined by X-ray structural analysis and then used for a docking study with jack bean urease enzyme. The obtained coordinates were further used for comprehensive DFT and Hirshfeld analyses. Evaluation of the combination of electrostatic interactions, dispersion effects, and total energy components suggests that the primary factor driving crystal stabilization is the electrostatic energy contribution. The molecular docking studies of VII reveal that the combination of acyl-thiourea with an amide functional group (known for their importance in artificial drug design) facilitated a good docking score of -8.7 Kcal/mol. Notable hydrogen bonding and CH π interactions were found. The presence of very efficient hydrogen bonding interactions with the active site of jack bean urease emphasizes that the molecule might serve as a rather potent actual inhibitor for urease enzymes. [Display omitted]