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

Caracelli, Ignez; Vega-Teijido, Maurício; Zukerman-Schpector, Júlio; Cezari, Maria Helena S.; Lopes, José Guilherme S.; Juliano, Luiz; Santos, Paulo S.; Comasseto, J. V.; Cunha, Rodrigo L. O. R.; Tiekink, Edward R. T.

doi:10.1016/j.molstruc.2012.01.008

Cited by 22 publications

(5 citation statements)

References 83 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…30 Cunha et al demonstrated that organotelluranes were more potent than AS-101 in the inhibition of cysteine proteases. 13,14 Piovan et al reported a structure−activity relationship of dihalogenated organochalcogenanes in inhibition of cathepsins V and S and that organotelluranes were superior to organoselenuranes. 15 The same behavior was observed for inhibition of thiol-dependent protein tyrosine phosphatases (PTP1B and the YopH) 16 and 20S proteasome, in this case a threonine protease.…”

Section: ■ Introductionmentioning

confidence: 99%

“…Tellurium is an important element from group 16 of the periodic table, and its chemical properties allow broad applications in both organic and inorganic chemistry, such as materials , and pharmacological science and medicinal chemistry . An intrinsic characteristic of this element is its wide range of oxidation states (−2 to +6), which allows the expansion of the Lewis octet rule, , giving the possibility of hypervalent species − · These compounds have potential applications in enzymatic inhibition − and some therapeutic applications …”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Investigation of Chemical Stability of Dihalogenated Organotelluranes in Organic–Aqueous Media: The Protagonism of Water

et al. 2018

View full text Add to dashboard Cite

The biological activity of tellurium compounds is closely related to the tellurium oxidation state or some of their structural features. Hypervalent dihalogenated organotelluranes 1-[butyl(dichloro)-λ-tellanyl]-2-(methoxymethyl)benzene (1a) and 1-[butyl(dibromide)-λ-tellanyl]-2-(methoxymethyl)benzene (1b) have been described as inhibitors of proteases (cysteine and threonine) and tyrosine phosphatases. However, poor attention has been given to their physicochemical properties. Here, a detailed investigation of the stability in water of these organotelluranes is reported using Te NMR analysis. Dihalogenated organotelluranes 1a and 1b were both stable in DMSO- d (from 25 to 75 °C), demonstrating their thermal stability. However, the addition of a phosphate buffer solution (pH 2-8) to 1a or 1b resulted in an immediate conversion to a new Te species, assumed to be the corresponding telluroxide. Similar behavior was observed in pure water, demonstrating the low chemical stability of these dihalogenated species in the presence of water. These results allow concluding that previous biological activity reported for dihalogenated organotelluranes 1a and 1b could be attributed to the corresponding derivatives from the reaction with water. In the same way as for AS-101, we demonstrated that organotelluranes 1a and 1b are not stable in aqueous solution. It suggests a proactive role of these organotelluranes in previously reported biological activity.

show abstract

Section: ■ Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Investigation of Chemical Stability of Dihalogenated Organotelluranes in Organic–Aqueous Media: The Protagonism of Water

et al. 2018

View full text Add to dashboard Cite

show abstract

“…The compound ammonium [trichloro(dioxoethylene- O , O ′) tellurate] (AS101; Figure A) is a potent immunomodulatory compound that exerts a variety of protective therapeutic applications in various in vivo models, , as well as in preclinical and clinical studies. − Much of the biological activity of AS-101 has been attributed to the pivotal Te IV atom and its specific chemical interactions with cysteine thiol residues. − On the basis of the unique Te IV –S chemical affinity, we previously demonstrated that AS-101 interacts by ligand substitution with 4 equiv of l -cysteine as a thiol model compound to form a stable NMR-detectable Te(Cys) 4 complex. Furthermore, AS-101 inhibited the cysteine proteases papain and cathepsin B, by inactivating the catalytic cysteines .…”

mentioning

confidence: 99%

Ligand-Substitution Reactions of the Tellurium Compound AS-101 in Physiological Aqueous and Alcoholic Solutions

et al. 2016

View full text Add to dashboard Cite

Since its first crystallization, the aqueous structure of the tellurium-containing experimental drug AS-101 has never been studied. We show that, under the aqueous conditions in which it is administered, AS-101 is subjected to an immediate ligand-substitution reaction with water, yielding a stable hydrolyzed oxide anion product that is identified, for the first time, to be TeOCl3 –. Studying the structure of AS-101 in propylene glycol (PG), an alcoholic solvent often used for the topical and oral administration of AS-101, revealed the same phenomenon of ligand-substitution reaction between the alcoholic ligands. Upon exposure to water, the PG-substituted product is also hydrolyzed to the same tellurium(IV) oxide form, TeOCl3 –.

show abstract

“…Effective inhibition will see optimal interactions of the tellurium ligand with the various subsites of the specific cathepsin under investigation [22,23]. As a continuation of investigations into the modes of association of putative tellurium-based drugs with a variety of cathepsins [43,44], herein a docking study of three previously described [21,45] 1,3diphenyl-4-(trichloro- 4 -tellanyl)but-2-en-1-one derivatives (1-3), Fig. 1b, with cathepsin S is reported.…”

Section: Introductionmentioning

confidence: 99%

Crystal structures and docking studies in cathepsin S of bioactive 1,3‐diphenyl‐4‐(trichloro‐λ4‐tellanyl)but‐2‐en‐1‐one derivatives

Maganhi

Caracelli

Zukerman-Schpector

et al. 2021

Journal of Molecular Structure

Self Cite

View full text Add to dashboard Cite

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

Cited by 22 publications

References 83 publications

Investigation of Chemical Stability of Dihalogenated Organotelluranes in Organic–Aqueous Media: The Protagonism of Water

Investigation of Chemical Stability of Dihalogenated Organotelluranes in Organic–Aqueous Media: The Protagonism of Water

Ligand-Substitution Reactions of the Tellurium Compound AS-101 in Physiological Aqueous and Alcoholic Solutions

Crystal structures and docking studies in cathepsin S of bioactive 1,3‐diphenyl‐4‐(trichloro‐λ4‐tellanyl)but‐2‐en‐1‐one derivatives

Contact Info

Product

Resources

About