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

Abstract

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.

Thais savignyi tissue extract: bioactivity, chemical composition, and molecular docking

“…Moreover, Saminathan et al. ( 2020 ) docked two pyrazoline-thiocyanatoethanone derivatives; 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) against the thymidylate kinase (ID: 4QGG). Their results showed that the two compounds formed different bonded interactions between compounds and TMK binding site residues with binding energies of −7.8 and −7.3 kJ/mol, respectively, for FSCN and ClSCN.…”

“…The interactions of the FSCN involved six hydrogen bonds with the Arg36, Arg48, Arg92, and Thr16 residues of TMK, while the compound ClSCN interacted with protein 4QGG through five hydrogen bonds with the residues Arg36, Arg92, and Thr16 (Saminathan et al. 2020 ).…”

Covalent organic frameworks with flexible side chains in hybrid PEMs enable highly efficient proton conductivity

“…1d) spectra. The appearance of the characteristic peak of C-H (2922, 2866 cm À1 ) 21 compared to Bd-SO 3 H belonged to side chains of Bd-C 3 -SO 3 H and Bd-C 4 -SO 3 H. The disappearance of the characteristic peaks of N-H (3425 cm À1 ) for the amine monomer, CHQO (2896 cm À1 ) and CQO (1639 cm À1 ) for the aldehyde monomer Tp, and the appearance of CQC (1572 cm À1 ) and C-N (1266 cm À1 ) for iCOFs proved the completion of the Schiff base polycondensation of iCOFs. In addition, the characteristic OQSQO (1076, 1027 cm À1 ) peak of -SO 3 H was also observed.…”

Spacer‐Engineered Ionic Channels in Covalent Organic Framework Membranes toward Ultrafast Proton Transport

“…[ 33,34 ] Compared with TpBd‐SO 3 H, TpBd‐C 3 ‐SO 3 H, and TpBd‐C 4 ‐SO 3 H give rise to new characteristic bands at ≈2930 cm −1 , which is assigned to the typical stretching vibration of C–H in side chain. [ 35 ] The thermostability of iCOFM was characterized by thermogravimetric analysis (TGA). As shown in Figure 3g, the crystalline and covalently crosslinked framework confers the TpBd‐SO 3 H with high thermal stability of 293.3 °C and the flexible side chains endow the TpBd‐C 3 ‐SO 3 H and TpBd‐C 4 ‐SO 3 H with initial degradation temperature of 261.7 °C, exceeding most conventional polymers.…”

“…Mater. 2023, 35,2211004 method. First, polyacrylonitrile (PAN) substrate with pore size of 10-20 nm was sandwiched by vacuum filter holder.…”