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

Show simple item record

dc.contributor.author Caracelli, Ignez
dc.contributor.author Vega-Teijido, Mauricio
dc.contributor.author Zukerman-Schpector, Julio
dc.contributor.author Cezari, Maria H. S. [UNIFESP]
dc.contributor.author Lopes, Jose G. S.
dc.contributor.author Juliano, Luiz [UNIFESP]
dc.contributor.author Santos, Paulo S.
dc.contributor.author Comasseto, Joao V.
dc.contributor.author Cunha, Rodrigo L. O. R. [UNIFESP]
dc.contributor.author Tiekink, Edward R. T.
dc.date.accessioned 2016-01-24T14:27:07Z
dc.date.available 2016-01-24T14:27:07Z
dc.date.issued 2012-04-11
dc.identifier http://dx.doi.org/10.1016/j.molstruc.2012.01.008
dc.identifier.citation Journal of Molecular Structure. Amsterdam: Elsevier B.V., v. 1013, p. 11-18, 2012.
dc.identifier.issn 0022-2860
dc.identifier.uri http://repositorio.unifesp.br/handle/11600/34797
dc.description.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 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. en
dc.description.sponsorship Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
dc.description.sponsorship Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.description.sponsorship Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorship Ministry of Higher Education (Malaysia)
dc.format.extent 11-18
dc.language.iso eng
dc.publisher Elsevier B.V.
dc.relation.ispartof Journal of Molecular Structure
dc.rights Acesso restrito
dc.subject Tellurium en
dc.subject Cathepsin B en
dc.subject X-ray crystal structure en
dc.subject Molecular modelling en
dc.subject Docking en
dc.subject Structure-activity relationships en
dc.title A tellurium-based cathepsin B inhibitor: Molecular structure, modelling, molecular docking and biological evaluation en
dc.type Artigo
dc.rights.license http://www.elsevier.com/about/open-access/open-access-policies/article-posting-policy
dc.contributor.institution Universidade Federal de São Carlos (UFSCar)
dc.contributor.institution Universidade de São Paulo (USP)
dc.contributor.institution Universidade Federal de São Paulo (UNIFESP)
dc.contributor.institution Univ Fed Juiz de Fora
dc.contributor.institution Universidade Federal do ABC (UFABC)
dc.contributor.institution Univ Malaya
dc.description.affiliation Univ Fed Sao Carlos, BioMat Dept Fis, BR-13565905 Sao Carlos, SP, Brazil
dc.description.affiliation Univ Estado São Paulo UNESP, Fac Ciencias, Dept Fis, Bauru, SP, Brazil
dc.description.affiliation Univ Fed Sao Carlos, Dept Quim, Lab Cristalog Estereodinam & Modelagem Mol, BR-13565905 Sao Carlos, SP, Brazil
dc.description.affiliation Universidade Federal de São Paulo, Escola Paulista Med, Dept Biofis, BR-0404420 São Paulo, Brazil
dc.description.affiliation Univ Fed Juiz de Fora, Inst Ciencias Exatas, Dept Quim, Juiz de Fora, MG, Brazil
dc.description.affiliation Univ São Paulo, Inst Quim, São Paulo, Brazil
dc.description.affiliation Univ Fed ABC UFABC, CCNH, Santo Andre, SP, Brazil
dc.description.affiliation Univ Malaya, Dept Chem, Kuala Lumpur 50603, Malaysia
dc.description.affiliationUnifesp Universidade Federal de São Paulo, Escola Paulista Med, Dept Biofis, BR-0404420 São Paulo, Brazil
dc.description.sponsorshipID CAPES: 808/2009
dc.description.sponsorshipID CNPq: 308116/2010-0
dc.description.sponsorshipID CNPq: 306532/2009-3
dc.description.sponsorshipID FAPESP: 06/56078-4
dc.description.sponsorshipID FAPESP: 07/52734-7
dc.description.sponsorshipID Ministry of Higher Education (Malaysia): UM.C/HIR/MOHE/SC/12
dc.identifier.doi 10.1016/j.molstruc.2012.01.008
dc.description.source Web of Science
dc.identifier.wos WOS:000302666300002



File

File Size Format View

There are no files associated with this item.

This item appears in the following Collection(s)

Show simple item record

Search


Browse

Statistics

My Account