A tellurium-based cathepsin B inhibitor: Molecular structure, modelling, molecular docking and biological evaluation

摘要: Abstract The crystallographically determined structure of biologically active 4,4-dichloro-1,3-diphenyl-4-telluraoct-2-en-1-one, 3 , shows the coordination geometry for Te to be distorted ψ-pentagonal bipyramidal based on a C 2 OCl (lone pair) donor set. Notable is presence an intramolecular axial Te⋯O(carbonyl) interaction, design element included reduce hydrolysis. Raman and molecular modelling studies indicate persistence interaction in solution (CHCl ) gas-phases, respectively. Docking 3′ (i.e. original less one chloride) with Cathepsin B reveals change configuration about vinyl bond, i.e. E from Z (crystal structure). This isomerism allows optimisation interactions complex which features covalent SGCys29 bond. Crucially, observed formation hypervalent Te⋯O as well O⋯H O hydrogen bond Gly27 Glu122 residues, Additional stabilisation afforded by combination spanning S1, S2, S1′ S2′ sub-sites B. greater experimental inhibitory activity compared analogues rationalised additional formed between His110 His111 residues occluding loop, serve hinder entrance site.