On the Self-Assembly of a Highly Selective Benzothiazole-Based TIM Inhibitor in Aqueous Solution

Hassan, Natalia; Gárate, M. Pilar; Sandoval, Tania E.; Espinoza, Luis; Piñeiro, Ángel; Ruso, Juan M.

doi:10.1021/la102916x

Cited by 12 publications

(5 citation statements)

References 70 publications

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“…The possible binding sites at the interface of TcTIM showed that fully flexible benzothiazoles were docked onto the dimer interface, purposing that the dimer disruption was not via Cys 15, as presented in last studies, but it could be carried out through the unstabilization of pi-pi interactions of two aromatic clusters present in the interface, enabling a novel alternative for rational SAR for drug design [392]. In addition, 3-(2-benzothiazolylthio)-propanesulfonic acid (BTS) has been described as a powerful and selective inhibitor of TcTIM [393].…”

Section: Triosephosphate Isomerase (Tim)mentioning

confidence: 99%

Targets and Patented Drugs for Chemotherapy of Chagas Disease in the Last 15 Years-Period

Duschak

2016

PRI

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In summary, loans on anti-Chagas disease agents focused to specific parasite targets as their metabolic pathways or specific enzymes will be summarized. Targets will also be specifically discussed. Patent literature collected and published from 2000 to 2015, alleging inhibitors for specific T. cruzi targets or trypanocidal activity was achieved over the search database from Delphion Research intellectual property network including international patents and the European patent office, Espacenet.

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Section: Triosephosphate Isomerase (Tim)mentioning

confidence: 99%

Targets and Patented Drugs for Chemotherapy of Chagas Disease in the Last 15 Years-Period

Duschak

2016

PRI

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“…The review of Alonso et al in 2006, focusing on applications and protocols of recent studies where docking calculations and molecular dynamics [31] simulations were combined to dock small molecules into protein receptors, is also remarkable. Recently, the MD simulations of the drug benzothiazole were performed to characterize the structure and dynamic behavior of the corresponding aggregates at several concentrations of the drug [30]. Also the structure and properties of the structures spontaneously formed within aqueous mixtures of the hydrogenated/fluorinated catanionic surfactant cetyltrimetylammonium perfluorooctanoate in the absence of counterions as a function of its concentration were investigated by computational study at room temperature [2b].…”

Section: Molecular Dynamic Studiesmentioning

confidence: 99%

“…Many of these drugs contain aromatic nuclei or are peptide nature. Examples of studied drugs are phenothiazine [19] and benzodiazepine [20] tranquiliziers, analgesics [21], peptide [22], antibiotics [23], tricyclic antidepressants [24], antihistamines [25], anticholinergics [26], -blockers [5,27], local anesthetics [28], non-steroidal antiinflammatory drugs [29], anticancer drugs [30]. Some of these structures can be observed in Fig.…”

Section: Introductionmentioning

confidence: 99%

Self-Assembly Drugs: From Micelles to Nanomedicine

Messina¹,

Besada-Porto²,

Ruso

2014

CTMC

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Self-assembly has fascinated many scientists over the past few decades. Rapid advances and widespread interest in the study of this subject has led to the synthesis of an ever-increasing number of elegant and intricate functional structures with sizes that approach nano-and mesoscopic dimensions. Today, it has grown into a mature field of modern science whose interfaces with many disciplines have provided invaluable opportunities for crossing boundaries for scientists seeking to design novel molecular materials exhibiting unusual properties, and for researchers investigating the structure and function of biomolecules. Consequently, self-assembly transcends the traditional divisional boundaries of science and represents a highly interdisciplinary field including nanotechnology and nanomedicine. Basically, self-assembly focuses on a wide range of discrete molecules or molecular assemblies and uses physical transformations to achieve its goals. In this Review, we present a comprehensive overview of the advances in the field of drug self-assembly and discuss in detail the synthesis, self-assembly behavior, and physical properties as well as applications. We refer the reader to past reviews dealing with colloidal molecules and colloidal self-assembly. In the first part, we will discuss, compare, and link the various bioinformatic procedures: Molecular Dynamics and Quantitative Structure Activity Relationship. The second section deals with the self-assembly behavior in more detail, in which we focus on several experimental techniques, selected according to the depth of knowledge obtained. The last part will review the advances in drug-protein assembly. Nature provides many examples of proteins that form their substrate binding sites by bringing together the component pieces in a process of self-assembly. We will focus in the understanding of physical properties and applications developing thereof.

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“…This is because the orientation presents great similarities with those found in complexes formed between aromatic molecules such as benzene, where the stabilization of this type of system has been rationalized based on models involving quadrupolar interactions [ 19 ]. Moreover, 3-(2-Benzothiazolylthio)-propanesulfonic acid (BTS) has been reported as a powerful and selective inhibitor of triosephosphate isomerase from Trypanosoma cruzi, the parasite that causes the Chagas disease [ 20 ]. In a previous work, we analyzed the interactions between BTS and lysozyme by differential scanning calorimetry and circular dichroism measurements [ 21 ].…”

Section: Introductionmentioning

confidence: 99%

Unraveling the Compositional and Molecular Features Involved in Lysozyme-Benzothiazole Derivative Interactions

et al. 2021

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In this work we present a computational analysis together with experimental studies, focusing on the interaction between a benzothiazole (BTS) and lysozyme. Results obtained from isothermal titration calorimetry, UV-vis, and fluorescence were contrasted and complemented with molecular docking and machine learning techniques. The free energy values obtained both experimentally and theoretically showed excellent similarity. Calorimetry, UV-vis, and 3D/2D-lig-plot analysis revealed that the most relevant interactions between BTS and lysozyme are based on a predominance of aromatic, hydrophobic Van der Waals interactions, mainly aromatic edge-to-face (T-shaped) π-π stacking interactions between the benzene ring belonging to the 2-(methylthio)-benzothiazole moiety of BTS and the aromatic amino acid residue TRP108 of the lysozyme receptor. Next, conventional hydrogen bonding interactions contribute to the stability of the BTS-lysozyme coupling complex. In addition, mechanistic approaches performed using elastic network models revealed that the BTS ligand theoretically induces propagation of allosteric signals, suggesting non-physiological conformational flexing in large blocks of lysozyme affecting α-helices. Likewise, the BTS ligand interacts directly with allosteric residues, inducing perturbations in the conformational dynamics expressed as a moderate conformational softening in the α-helices H1, H2, and their corresponding β-loop in the lysozyme receptor, in contrast to the unbound state of lysozyme.

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On the Self-Assembly of a Highly Selective Benzothiazole-Based TIM Inhibitor in Aqueous Solution

Cited by 12 publications

References 70 publications

Targets and Patented Drugs for Chemotherapy of Chagas Disease in the Last 15 Years-Period

Targets and Patented Drugs for Chemotherapy of Chagas Disease in the Last 15 Years-Period

Self-Assembly Drugs: From Micelles to Nanomedicine

Unraveling the Compositional and Molecular Features Involved in Lysozyme-Benzothiazole Derivative Interactions

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