Octa‐<i>O</i>‐bis‐(<i>R,R</i>)‐Tartarate Ditellurane (SAS)—a Novel Bioactive Organotellurium(IV) Compound: Synthesis, Characterization, and Protease Inhibitory Activity

Yosef, Sigal; Brodsky, Miri; Sredni, Benjamin; Albeck, Amnon; Albeck, Michael

doi:10.1002/cmdc.200700155

Cited by 36 publications

(17 citation statements)

References 46 publications

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“…Te-SG [33,34]. The difference in Cathepsin inhibition values exhibited by the same compound arise owing to specific features of the various sub-sites in the enzyme which are responsible for the specificity of the protease [35,36].…”

Section: Decane (1) (3e)-2-chloro-3-(chloromethylidene)-2-(4-methoxymentioning

confidence: 99%

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

Caracelli

Maganhi

Cardoso

et al. 2017

Zeitschrift Für Kristallographie - Crystalline Materials

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Abstract. The molecular structures of the halotelluroxetanes pMeOC6H4Te(X)[C(=C(H)Xꞌ)C(CH2)nO], X = Xꞌ = Cl and n = 6 (1) and X = Cl, Xꞌ = Br and n = 5 (4), show similar binuclear aggregates sustained by { … Te-O}2 cores comprising covalent Te-O and secondary Te⋯O interactions. The resulting C2ClO2(lone-pair) sets define pseudo-octahedral geometries. In each structure, C-X⋯(arene) interactions lead to supramolecular layers. Literature studies have shown these and related compounds (i.e. 2: X = Xꞌ = Cl and n = 5; 3: X = Xꞌ = 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 telluriumbound X atoms) 1ꞌ-3ꞌ (note 3ꞌ = 4ꞌ) 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 … π interaction with the phenyl ring; for 1ꞌ 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.

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Section: Decane (1) (3e)-2-chloro-3-(chloromethylidene)-2-(4-methoxymentioning

confidence: 99%

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

Caracelli

Maganhi

Cardoso

et al. 2017

Zeitschrift Für Kristallographie - Crystalline Materials

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“…In particular, the irreversible inhibition activity of AS101 was described and, subsequently, an extensive study of other biological properties of this compound ensued. [8][9][10][11] As cathepsin B is involved in a number of human diseases, [12][13][14] the development of selective inhibitors of cathepsin B has become a mainstay in the search of chemotherapeutic agents. 15 Recently, Cunha et al 16,17 presented a series of eight organotellurium(IV) compounds which exhibited more effective inhibition of Cathepsin B compared with AS101.…”

Section: Introductionmentioning

confidence: 99%

2-chlorovinyl tellurium dihalides, (p-tol)Te[C(H)=C(Cl)Ph]X2 for X = Cl, Br and I: variable coordination environments, supramolecular structures and docking studies in cathepsin B

Caracelli¹,

Zukerman-Schpector²,

Maganhi³

et al. 2010

J. Braz. Chem. Soc.

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Os estudos cristalográficos mostram que o poliedro de coordenação ao redor do átomo de Te, em cada um dos compostos (p-tol)Te[C(H)=C(Cl)Ph]X 2 , com X = Cl (1), Br (2) e I (3), é uma Ψ-bipirâmide pentagonal distorcida. O grupo vinil em (1) adota uma configuração E o que impede a formação de uma interação intramolecular Te … Cl e em seu lugar é encontrada uma interação intramolecular Te … p. O poliedro de coordenação é formado por um arranjo linear Cl-Te-Cl com o plano pentagonal definido por dois átomos de C dos substituintes orgânicos, um contato intermolecular Te … Cl, uma interação Te … p e um par isolado de elétrons estereoquimicamente ativo. Geometrias de coordenação semelhantes são encontradas para as estruturas com X = Br (2) e I (3), mas a interação p é substituída por uma interação intramolecular Te … Cl devido à adoção de uma configuração Z em torno da ligação vinil. As diferenças nas estruturas são facilmente explicadas em termos de efeitos eletrônicos. Estudos de docking em catepsina B com (1')-(3'), ou seja, compostos 1 a 3 em que há um haleto a menos ligado ao átomo de Te, mostram que há uma ligação eficiente com a proteína pela formação da ligação covalente Te-S Cys29 com a estabilização proporcionada por uma combinação de interações N-H … p, C-H … p e Cl vinyl … H. Estes resultados são comparáveis aos obtidos com inibidores conhecidos da catepsina B o que sugere que os compostos estudados têm potencial atividade biológica.Crystallography shows that the Te atom in each of (p-tol)Te[C(H)=C(Cl)Ph]X 2 , for X = Cl (1), Br (2) and I (3), is within a distorted Ψ-pentagonal bipyramidal geometry. An E configuration for the vinyl group in (1) precludes the formation of an intramolecular Te … Cl interaction so that an intramolecular Te … p interaction is found instead. The coordination environment features a linear Cl-Te-Cl arrangement with the pentagonal plane defined by the two C atoms of the organic substituents, an intermolecular Te … Cl contact, a Te … p interaction and a stereochemically active lone pair of electrons. In the X = Br (2) and I (3) structures, similar coordination geometries are found but the Te … p contact is replaced by an intramolecular Te … Cl contact owing to the adoption of a Z configuration about the vinyl bond. The differences in structure are readily explained in terms of electronic effects. Docking studies of cathepsin B with (1')-(3'), i.e. 1-3 less one Te-bound halide, show efficient binding through the agency of covalent Te-S Cys29 bonds with stabilization afforded by a combination of N-H … p, C-H … p and Cl vinyl … H interactions. These results comparable favorably with known inhibitors of cathepsin B suggesting the title compounds have potential biological activity.Keywords: organotellurium-dihalides, docking studies, cathepsin B, crystal structures, supramolecular arrangements 2-Chlorovinyl Tellurium Dihalides, (p-tol)Te[C(H)=C(Cl)Ph]X 2 for X = Cl, Br and I J. Braz. Chem. Soc. 2156 IntroductionOrganotellurium halides comprise an interesting class of compounds owing...

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“…Indeed, we demonstrated that AS101 and SAS specifically inactivate cysteine proteases, while exhibiting no effect on the other families of serine-, aspartic-and metalloproteases, in good agreement with predictions based on their unique Te IV -thiol chemistry. Furthermore, the proteolytic activity of the inactivated cysteine proteases could be recovered by reducing agents such as NaBH 4 , further supporting the suggestion that the inactivation process involves oxidation of the catalytic thiol to a disulfide [8,9].…”

Section: Biological Activity Of Tellurium Compoundsmentioning

confidence: 67%

“…The compounds exerting the most pronounced biological activities are Te IV valences, including AS101 [ammonium trichloro (dioxoethylene-O,O_)tellurate] [7,8], and SAS [octa-O-bis-(R,R)-tartarate ditellurane] [8,9]. Our studies have pioneered a new area, demonstrating the potency of inorganic Te IV compounds in biology.…”

Section: Biological Activity Of Tellurium Compoundsmentioning

confidence: 93%

The effect of the novel tellurium compound AS101 on autoimmune diseases

Halpert

Sredni

2014

Autoimmunity Reviews

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Octa‐O‐bis‐(R,R)‐Tartarate Ditellurane (SAS)—a Novel Bioactive Organotellurium(IV) Compound: Synthesis, Characterization, and Protease Inhibitory Activity

Cited by 36 publications

References 46 publications

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

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

2-chlorovinyl tellurium dihalides, (p-tol)Te[C(H)=C(Cl)Ph]X2 for X = Cl, Br and I: variable coordination environments, supramolecular structures and docking studies in cathepsin B

The effect of the novel tellurium compound AS101 on autoimmune diseases

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