Crystallographic and docking (Cathepsins B, K, L and S) studies on bioactive halotelluroxetanes

Author(s)

Caracelli, Ignez ^[1] ; Maganhi, Stella H. ^[2] ; Cardoso, Josiane de Oliveira ^[1] ; Cunha, Rodrigo L. O. R. ^[3] ; Vega-Teijido, Mauricio Angel ^{[4, 5]} ; Zukerman-Schpector, Julio ^[4] ; Tiekink, Edward R. T. ^[6]

Affiliation

^[1] Univ Fed Sao Carlos, Dept Fis, BioMat, CP 676, BR-13565905 Sao Carlos, SP - Brazil

^[2] Univ Fed Sao Carlos, Programa Posgrad Biotecnol, BioMat, CP 676, BR-13565905 Sao Carlos, SP - Brazil

^[3] Fed Univ ABC, Ctr Nat Sci & Humanities, BR-09210180 Santo Andre, SP - Brazil

^[4] Univ Fed Sao Carlos, Dept Quim, Lab Cristalog Estereodinam & Modelagem Mol, CP 676, BR-13565905 Sao Carlos, SP - Brazil

^[5] Univ Republica, Fac Quim, DETEMA, CCBG, Montevideo - Uruguay

^[6] Sunway Univ, Res Ctr Crystalline Mat, Sch Sci & Technol, Bandar Sunway 47500, Selangor Darul - Malaysia

• Document type: Journal article
• Source: ZEITSCHRIFT FUR KRISTALLOGRAPHIE-CRYSTALLINE MATERIALS; v. 233, n. 2, p. 113-124, FEB 2018.
• Web of Science Citations: 0

Abstract

The molecular structures of the halotelluroxetanes p-MeOC6H4Te(X){[}C(= C(H)X')C(CH2)(n)O], X = X' = Cl and n = 6 (1) and X = Cl, X' = Br and n = 5 (4), show similar binuclear aggregates sustained by [center dot center dot center dot Te-O](2) cores comprising covalent Te-O and secondary Te center dot center dot center dot O interactions. The resulting C2ClO2 (lone-pair) sets define pseudooctahedral geometries. In each structure, C-X center dot center dot center dot pi(arene) interactions lead to supramolecular layers. Literature studies have shown these and related compounds (i.e. 2: X = X' = Cl and n = 5; 3: X = X' = Br and n = 5) to inhibit Cathepsins B, K, L and S to varying extents. Molecular docking calculations have been conducted on ligands (i.e. cations derived by removal of the tellurium-bound X atoms) 1'-3' (note 3' = 4') enabling correlations between affinity for sub-sites and inhibition. The common feature of all docked complexes was the formation of a Te-S covalent bond with cysteine residues, the relative stability of the ligands with an E-configuration and the formation of a C-O center dot center dot center dot pi interaction with the phenyl ring; for 1' the Te-S covalent bond was weak, a result correlating with its low inhibition profile. At the next level differences are apparent, especially with respect to the interactions formed by the organic-ligand-bound halides. While these atoms do not form specific interactions in Cathepsins B and K, in Cathepsin L, these halides are involved in C-O center dot center dot center dot X halogen bonds. (AU)

• FAPESP's process: 12/22524-9 - Synthesis, characterization and docking studies of controlled drug delivery systems for drugs and potential drugs using chitosan as a carrier
• Grantee: Stella Hernandez Maganhi
• Support Opportunities: Scholarships in Brazil - Post-Doctoral