Synthesis, structural, DFT investigations and antibacterial activity assessment of pyrazoline‐thiocyanatoethanone derivatives as thymidylate kinase inhibitors

• Published in: Journal of the Chinese Chemical Society (Taipei) Vol. 67; no. 6; pp. 1100 - 1112
• Main Authors: Saminathan, Murugavel, Kanagarajan, Saranya, Chandrasekaran, Ravikumar, Sivasubramaniyan, Archana, Raja, Ranganathan, Alagusundaram, Ponnusamy
• Format: Journal Article
• Language: English
• Published: Weinheim Wiley‐VCH Verlag GmbH & Co. KGaA 01-06-2020; Wiley Subscription Services, Inc
• Subjects: antibacterial activities; Antibacterial materials; Bacterial diseases; Benzene; Crystal structure; DFT; Hydrocarbons; Kinases; NMR; Nuclear magnetic resonance; pharmacological, molecular docking; Proteins; Pyrazole; Pyrazoline; Synthesis; thiocyanatoethanone
• ISSN: 0009-4536; 2192-6549
• DOI: 10.1002/jccs.201900363

Two novel compounds 1‐(5‐[4‐fluorophenyl]‐3‐phenyl‐4,5‐dihydro‐1H‐pyrazol‐1‐yl)‐2‐thiocyanatoethanone (FSCN) and 1‐(5‐[4‐chlorophenyl]‐3‐phenyl‐4,5‐dihydro‐1H‐pyrazol‐1‐yl)‐2‐thiocyanatoethanone (ClSCN) were synthesized and characterized by SC‐XRD, 1H NMR, 13C NMR, FTIR, and UV methods. The X‐ray diffraction studies were utilized to prove the 3D crystal structures of FSCN and ClSCN. In both the compounds, the packing is mostly driven by CH⋯N, CH⋯O, and CH⋯π (benzene ring as an acceptor) interactions. In ClSCN, additionally, the π⋯π interaction is observed between the pyrazole ring of one molecule and the benzene ring of the other molecule. The experimental values were compared with the results of DFT/B3LYP/6‐311G++(d,p) theoretical computations. The pharmacological screening for FSCN and ClSCN was performed using molinspiration and PreADMET web server. To analyze antibacterial inhibition of the synthesized ligands and Ciprofloxacin (control drug) were interacted with antibacterial protein Thymidylate Kinase (TMK) (PDB ID: 4QGG) with the help of AutoDock Vina tool. The ADMET and docking results of FSCN and ClSCN pointed out the better drug likeness nature and good inhibition behavior with TMK protein. The antibacterial in vitro studies suggested that FSCN compound inhibited well with antibacterial strains than that of ClSCN. The current investigation suggests that with further improvements, our compounds could be preferred as substitute medicine for bacterial diseases.
Antibacterial activity of newly synthesized pyrazoline fused thiocyanatoethanone derivatives as thymidylate kinase inhibitors.