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

dc.contributorUniversidade Estadual Paulista (UNESP)
dc.creatorCaracelli, Ignez
dc.creatorVega-Teijido, Mauricio
dc.creatorZukerman-Schpector, Julio
dc.creatorCezari, Maria H. S.
dc.creatorLopes, Jose G. S.
dc.creatorJuliano, Luiz
dc.creatorSantos, Paulo S.
dc.creatorComasseto, Joao V.
dc.creatorCunha, Rodrigo L. O. R.
dc.creatorTiekink, Edward R. T.
dc.date2014-05-20T13:26:18Z
dc.date2016-10-25T16:46:29Z
dc.date2014-05-20T13:26:18Z
dc.date2016-10-25T16:46:29Z
dc.date2012-04-11
dc.date.accessioned2017-04-05T20:05:06Z
dc.date.available2017-04-05T20:05:06Z
dc.identifierJournal of Molecular Structure. Amsterdam: Elsevier B.V., v. 1013, p. 11-18, 2012.
dc.identifier0022-2860
dc.identifierhttp://hdl.handle.net/11449/8448
dc.identifierhttp://acervodigital.unesp.br/handle/11449/8448
dc.identifier10.1016/j.molstruc.2012.01.008
dc.identifierWOS:000302666300002
dc.identifierhttp://dx.doi.org/10.1016/j.molstruc.2012.01.008
dc.identifier.urihttp://repositorioslatinoamericanos.uchile.cl/handle/2250/856813
dc.descriptionThe 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 psi-pentagonal bipyramidal based on a C2OCl3(lone pair) donor set. Notable is the presence of an intramolecular axial Te center dot center dot center dot O (carbonyl) interaction, a design element included to reduce hydrolysis. Raman and molecular modelling studies indicate the persistence of the Te center dot center dot center dot O(carbonyl) interaction in the solution (CHCl3) and gasphases, respectively. Docking studies of 3' (i.e. original 3 less one chloride) with Cathepsin B reveals a change in the configuration about the vinyl C = C bond. i.e. to E from Z (crystal structure). This isomerism allows the optimisation of interactions in the complex which features a covalent Te-SGCys29 bond. Crucially, the E configuration observed for 3' allows for the formation of a hypervalent Te center dot center dot center dot O interaction as well as an O center dot center dot center dot H-O hydrogen bond with the Gly27 and Glu122 residues, respectively. Additional stabilisation is afforded by a combination of interactions spanning the S1, S2, S1' and S2' sub-sites of Cathepsin B. The greater experimental inhibitory activity of 3 compared with analogues is rationalised by the additional interactions formed between 3' and the His110 and His111 residues in the occluding loop, which serve to hinder the entrance to the active site. (C) 2012 Elsevier B.V. All rights reserved.
dc.descriptionCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
dc.descriptionConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.languageeng
dc.publisherElsevier B.V.
dc.relationJournal of Molecular Structure
dc.rightsinfo:eu-repo/semantics/closedAccess
dc.subjectTellurium
dc.subjectCathepsin B
dc.subjectX-ray crystal structure
dc.subjectMolecular modelling
dc.subjectDocking
dc.subjectStructure-activity relationships
dc.titleA tellurium-based cathepsin B inhibitor: Molecular structure, modelling, molecular docking and biological evaluation
dc.typeOtro


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