A combined crystallographic and theoretical investigation of noncovalent interactions in 1,3,4-oxadiazole-2-thione- N -Mannich derivatives: in vitro bioactivity and molecular docking.
Lamya H Al-WahaibiKowsalya AlagappanRosa Maria GomilaOlivier BlacqueAntonio FronteraMaría Judith PercinoAli A El-EmamSubbiah ThamotharanPublished in: RSC advances (2023)
Two 1,3,4-oxadiazole-2-thione- N -Mannich derivatives, specifically 5-(4-chlorophenyl)-3-[(2-trifluoromethylphenylamino)methyl]-1,3,4-oxadiazole-2(3 H )-thione (1) and 5-(4-chlorophenyl)-3-[(2,5-difluorophenylamino)methyl]-1,3,4-oxadiazole-2(3 H )-thione (2), were synthesized and then characterized by elemental analysis and NMR ( 1 H and 13 C) spectroscopy and the single crystal X-ray diffraction method. The formed weak intermolecular interactions in the solid-state structures of these derivatives were thoroughly investigated utilizing a variety of theoretical tools such as Hirshfeld surface analysis and quantum theory of atoms in molecules (QTAIM). Furthermore, the CLP-PIXEL and density functional theory calculations were used to study the energetics of molecular dimers. Numerous weak intermolecular interactions such as C-H⋯S/Cl/F/π interactions, a directional C-Cl⋯Cl halogen bond, π-stacking, type C-F⋯F-C contact and a short F⋯O interaction, help to stabilize the crystal structure of 1. Crystal structure 2 also stabilizes with several weak intermolecular contacts, including N-H⋯S, C-H⋯N//Cl/F interactions, a highly directional C1-Cl1⋯C(π) halogen bond and C(π)⋯C(π) interaction. In vitro antimicrobial potency of compounds 1 and 2 was assessed against various Gram-positive and Gram-negative bacterial strains and the pathogenic yeast-like Candida albicans . Both compounds showed marked activity against all tested Gram-positive bacteria and weak activity against Escherichia coli and lacked inhibitory activity against Pseudomonas aeruginosa . In addition, compounds 1 and 2 displayed good in vitro anti-proliferative activity against hepatocellular carcinoma (HepG-2) and mammary gland breast cancer (MCF-7) cancer cell lines. Molecular docking studies revealed the binding modes of title compounds at the active sites of prospective therapeutic targets.
Keyphrases
- molecular docking
- gram negative
- crystal structure
- solid state
- density functional theory
- escherichia coli
- molecular dynamics simulations
- candida albicans
- multidrug resistant
- molecular dynamics
- high resolution
- pseudomonas aeruginosa
- biofilm formation
- energy transfer
- staphylococcus aureus
- magnetic resonance
- cystic fibrosis
- computed tomography
- magnetic resonance imaging
- single molecule
- young adults
- mass spectrometry
- structure activity relationship
- klebsiella pneumoniae
- electron microscopy
- squamous cell
- electron transfer
- dual energy