Tetrahydroindoles as Multipurpose Screening Compounds and Novel Sirtuin Inhibitors

Indoles are privileged structures in medicinal and bioorganic chemistry that are particularly well suited to serve as platforms for diversity. Among many other therapeutic areas, the indole scaffold has been used to design aromatic compounds useful to interfere with enzymes engaged in the regulation of substrate acylation status, such as sirtuins. However, the planarity of the indole ring is not necessarily optimal for all target enzymes, especially when functionalization with aromatic side chains is required. Replacement of flat scaffolds by nonplanar molecular cores dominated by sp³ hybridization is a common strategy to avoid the disadvantages associated with poor solubility and high promiscuity, while covering less-well-explored areas of chemical space. Thus, we synthesized fragment-like tetrahydroindoles suitable for fragment-based drug discovery as well as a well-characterized small library intended as multipurpose screening compounds. For proof of principle, these compounds were screened against sirtuins 1–3, enzymes known to be addressable by indoles. We found that 2,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-1H-indole-3-carboxamides are potent and selective SIRT2 inhibitors. Compound 16 t displayed an IC₅₀ value of 0.98 μm and could serve as exquisite starting point for hit-to-lead profiling.     

Electrocatalytic Reduction of CO2 to Ethylene by Molecular Cu‐Complex Immobilized on Graphitized Mesoporous Carbon

The electrochemical reduction of carbon dioxide (CO₂) to hydrocarbons is a challenging task because of the issues in controlling the efficiency and selectivity of the products. Among the various transition metals, copper has attracted attention as it yields more reduced and C2 products even while using mononuclear copper center as catalysts. In addition, it is found that reversible formation of copper nanoparticle acts as the real catalytically active site for the conversion of CO₂ to reduced products. Here, it is demonstrated that the dinuclear molecular copper complex immobilized over graphitized mesoporous carbon can act as catalysts for the conversion of CO₂ to hydrocarbons (methane and ethylene) up to 60%. Interestingly, high selectivity toward C2 product (40% faradaic efficiency) is achieved by a molecular complex based hybrid material from CO₂ in 0.1 m KCl. In addition, the role of local pH, porous structure, and carbon support in limiting the mass transport to achieve the highly reduced products is demonstrated. Although the spectroscopic analysis of the catalysts exhibits molecular nature of the complex after 2 h bulk electrolysis, morphological study reveals that the newly generated copper cluster is the real active site during the catalytic reactions.     

Chromophore-Free Sealing and Repair of Soft Tissues Using Mid-Infrared Light-Activated Biosealants

Poor strength, infection, leakage, long procedure times, and inflammation limit the efficacy of common tissue sealing devices in surgeries and trauma. Light-activated sealing is attractive for tissue sealing and repair, and can be facilitated by the generation of local heat following absorption of nonionizing laser energy by chromophores. Here, the inherent ability of biomaterials is exploited to absorb nonionizing, mid-infrared (midIR) light in order to engender rapid photothermal sealing and repair of soft tissue wounds. In this approach, the biomaterial simultaneously acts as a photothermal convertor as well as a biosealant, which dispenses the need for exogeneous light-absorbing nanoparticles or dyes. Biomechanical recovery, mathematical modeling, histopathology analyses, tissue strain mapping using digital imaging correlation, and visualization of the biosealant-tissue interface using hyperspectral imaging indicate superior performance of midIR sealing in live mice compared to conventional sutures and glue. The midIR-biosealant approach demonstrates rapid sealing of soft tissues, improves cosmesis, lowers potential for scarring, obviates safety concerns because of the nonionizing light used, and allows adoption of a wide diversity of biomaterials. Taken together, the studies demonstrate a novel advance both in biomaterials for surgical sealing along with the use of nonionizing midIR light, with high potential for clinical translation.     

Partitioning of predominant lipophilic bioactives (squalene, α-tocopherol and β-sitosterol) during olive oil processing

The partitioning of predominant lipophilic olive bioactives (squalene, β-sitosterol and α-tocopherol) in olive oil processing was studied for the first time using common integrated olive milling plant. 7% of the oil and 5% of the squalene present in the olives was lost in the last pomace. β-sitosterol and α-tocopherol, which are mainly concentrated in the seed of the olive fruit, was recovered in virgin olive oil to a lesser extent (66%, 67%) while 10% were lost in last pomace. Thus, the loss of β-sitosterol and α-tocopherol was higher than that of squalene and oil, due to nonrecovered bound forms. 19% of the α-tocopherol and 21% of the β-sitosterol loss was unaccounted for, which can be attributed to degradation of α-tocopherol and incomplete recovery of sterols from the olive and pomace matrices. This study provides a basis for process development studies.     

Visualizing for the Non‐Visual: Enabling the Visually Impaired to Use Visualization

The majority of visualizations on the web are still stored as raster images, making them inaccessible to visually impaired users. We propose a deep‐neural‐network‐based approach that automatically recognizes key elements in a visualization, including a visualization type, graphical elements, labels, legends, and most importantly, the original data conveyed in the visualization. We leverage such extracted information to provide visually impaired people with the reading of the extracted information. Based on interviews with visually impaired users, we built a Google Chrome extension designed to work with screen reader software to automatically decode charts on a webpage using our pipeline. We compared the performance of the back‐end algorithm with existing methods and evaluated the utility using qualitative feedback from visually impaired users.     

Combination of vegetable soup and glucan demonstrates synergistic effects on macrophage-mediated immune responses

Vegetable soup (VS), a plant-based functional food, has been used as a traditional folk medicine and is attracting attention for its ability to enhance the immune response. β-Glucan, a well-established and effective immunomodulator, has synergistic effects when used in combination with some bioactive compounds. In the present study, we aimed to evaluate the synergistic immunomodulatory effects of the combination of VS and β-glucan on macrophage-mediated immune responses. β-Glucan was demonstrated to synergistically enhance the VS-stimulated immune response, including the production of interleukin-6, tumor necrosis factor-α, and nitric oxide, mainly through the mitogen-activated protein kinase pathway in macrophages. In addition, this combination has the potential for further development in functional foods with immune-enhancing activity.Supplementary InformationThe online version contains supplementary material available at 10.1007/s10068-021-00888-x.