Green synthesis, characterization, and therapeutic potential of 2-(Thiophen-2-ylmethylene)malononitrile: Insights into molecular interactions with cyclooxygenase-2 (COX-2)
subject: Cyclooxygenase-2; In vitro study; Molecular dynamics simulation; Spectroscopic characterization; Topological and Hirshfeld surface analysis
description: A novel bioactive molecule, 2-(thiophen-2-ylmethylene)malononitrile, was synthesized via a green chemistry approach using thiophene-2-carbaldehyde and malononitrile under sonication in ethanol. The compound was characterized by UV-visible, H NMR, C NMR, HR-MS spectroscopy, and single-crystal XRD techniques, confirming its structural integrity. Computational studies revealed its chemical reactivity, including molecular electrostatic potential (MEP), Mulliken charges, and frontier molecular orbitals (FMO). At the same time, time-dependent DFT (TD-DFT) highlighted key electronic transitions across diverse solvents. Advanced analyses, such as Hirshfeld surface mapping and electron localization functions, identified critical intermolecular interactions involving H?N, N?H, and C?H contacts. Molecular docking with Cyclooxygenase-2 (COX-2, PDB ID: 6 2j) revealed strong binding affinity, further supported by molecular dynamics simulations demonstrating complex stability through RMSD, Rg, SASA, and hydrogen bond evaluations. The compound's anti-inflammatory potential was validated in vivo using a carrageenan-induced paw oedema model in rats, showing comparable efficacy to standard drugs. This study highlights the sustainable synthesis and therapeutic promise of 2-(thiophen-2-ylmethylene)malononitrile for pharmaceutical applications. 2025 Elsevier B.V.
creator: Tabassum, Sumaiya; Basha, A. Aathif; Govindaraju, Santhosh; Kubaib, Attar
source: Journal of Molecular Structure;Volume;1346;Issue;;Article No.;143186;
publisher: Elsevier B.V.
date: 01-01-2025
rights: Restricted Access; Hardcopy may be available in the library
relation: ISSN: 222860; CODEN: JMOSB
format: online
language: English
type: Article
coverage: Tabassum S., Department of Chemistry, Surana College - Autonomous, South End Road, Karnataka, Bengaluru, 560004, India; Basha A.A., Department of Physics, Islamiah College (Autonomous), Tamilnadu, Vaniyambadi, 635752, India, Department of Physics, KNS Institute of Technology, Karnataka, Bangalore, 560 064, India; Govindaraju S., Department of Sciences and Humanities, Christ University, Mysore Road, Karnataka, Bengaluru, 560074, India; Kubaib A., Department of Chemistry, Islamiah College (Autonomous), Tamilnadu, Vaniyambadi, 635752, India