Design and Synthesis of Multi-Functional Ligands through Hantzsch Reaction: Targeting Ca2+ Channels, Activating Nrf2 and Possessing Cathepsin S Inhibitory, and Antioxidant Properties

This work relates to the design and synthesis of a series of novel multi-target directed ligands (MTDLs), i.e., compounds 4a–l, via a convenient one-pot three-component Hantzsch reaction. This approach targeted calcium channel antagonism, antioxidant capacity, cathepsin S inhibition, and interference with Nrf2 transcriptional activation. Of these MTDLs, 4i emerged as a promising compound, demonstrating robust antioxidant activity, the ability to activate Nrf2-ARE pathways, as well as calcium channel blockade and cathepsin S inhibition. Dihydropyridine 4i represents the first example of an MTDL that combines these biological activities.This work was supported by the Regional Council of Franche-Comté (2022Y-13659 and 13660 ACCURATE PROJECT).Peer reviewe

Exploring the Potential of Sulfonamide-Dihydropyridine Hybrids as Multitargeted Ligands for Alzheimer’s Disease Treatment

Alzheimer’s disease (AD) is a multifactorial neurodegenerative disease that has a heavy social and economic impact on all societies and for which there is still no cure. Multitarget-directed ligands (MTDLs) seem to be a promising therapeutic strategy for finding an effective treatment for this disease. For this purpose, new MTDLs were designed and synthesized in three steps by simple and cost-efficient procedures targeting calcium channel blockade, cholinesterase inhibition, and antioxidant activity. The biological and physicochemical results collected in this study allowed us the identification two sulfonamide-dihydropyridine hybrids showing simultaneous cholinesterase inhibition, calcium channel blockade, antioxidant capacity and Nrf2-ARE activating effect, that deserve to be further investigated for AD therapy.This work was supported by the Regional Council of Franche-Comté (2022Y-13659 and 13660 Accurate Project).Peer reviewe

Supporting information : Biginelli Reaction Synthesis of Novel Multitarget- Directed Ligands with Ca2+ Channel Blocking Ability, Cholinesterase Inhibition, Antioxidant Capacity, and Nrf2 Activation

Peer reviewe

Supporting information : Exploring the Potential of Sulfonamide-Dihydropyridine Hybrids as Multitargeted Ligands for Alzheimer’s Disease Treatment

Peer reviewe

Demonstration of a parity-time symmetry breaking phase transition using superconducting and trapped-ion qutrits

Scalable quantum computers hold the promise to solve hard computational problems, such as prime factorization, combinatorial optimization, simulation of many-body physics, and quantum chemistry. While being key to understanding many real-world phenomena, simulation of non-conservative quantum dynamics presents a challenge for unitary quantum computation. In this work, we focus on simulating non-unitary parity-time symmetric systems, which exhibit a distinctive symmetry-breaking phase transition as well as other unique features that have no counterpart in closed systems. We show that a qutrit, a three-level quantum system, is capable of realizing this non-equilibrium phase transition. By using two physical platforms - an array of trapped ions and a superconducting transmon - and by controlling their three energy levels in a digital manner, we experimentally simulate the parity-time symmetry-breaking phase transition. Our results indicate the potential advantage of multi-level (qudit) processors in simulating physical effects, where additional accessible levels can play the role of a controlled environment.Comment: 14 pages, 9 figure

Uv-visible characterization of gold exchanged in beta zeolite

info:eu-repo/semantics/publishe

Comparison of gold and silver species supported and incorporated into mordenites

info:eu-repo/semantics/nonPublishe

Decadal Stability of Macrobenthic Zonation along the Estuarine Gradient in the Ob Bay, the Largest Siberian Estuary

The Siberian Arctic Shelf is an area of increasing anthropogenic activity and is predicted to be significantly impacted by climate change. Accordingly, there is an increased demand for baseline knowledge on the scales of natural spatiotemporal variation of different ecosystem components. The study aimed to investigate the spatial variability of macrobenthic communities and associated abiotic forcing in the Ob Bay, a major Arctic estuary. Four main zones of macrobenthic communities were identified: a brackish-water zone in the upper part of the estuary, which was divided into two subzones according to the dominant species; a transition zone at the mouth of the Ob Bay; and a marine zone. This zonation remained stable during the study period (2013–2019) and corresponded well with previous studies in the area. The large-scale variation in macrobenthic communities was related mainly to two independent drivers: salinity and sediment type. The within-zone variation increased with the number of coexisting species, but no temporal trends could be assessed. The study highlights the need to account for the small-scale heterogeneity of benthic communities to understand ecosystem functioning and long-term dynamics, particularly in areas where environmental conditions vary markedly

Biginelli Reaction Synthesis of Novel Multitarget-Directed Ligands with Ca2+ Channel Blocking Ability, Cholinesterase Inhibition, Antioxidant Capacity, and Nrf2 Activation

Novel multitarget-directed ligands BIGI 4a-d and BIGI 5a-d were designed and synthesized with a simple and cost-efficient procedure via a one-pot three-component Biginelli reaction targeting acetyl-/butyrylcholinesterases inhibition, calcium channel antagonism, and antioxidant ability. Among these multitarget-directed ligands, BIGI 4b, BIGI 4d, and BIGI 5b were identified as promising new hit compounds showing in vitro balanced activities toward the recognized AD targets. In addition, these compounds showed suitable physicochemical properties and a good druglikeness score predicted by Data Warrior software

Efficiency estimation of super-viscous oil recovery by in-situ catalytic upgrading in cyclic steam stimulation: from laboratory screening to numerical simulation

The article provides an overview of ion-modified waterflooding technology, also known as low salinity, controlled salinity, or Smart water. This technology is currently considered one of the most promising approaches in the development of oil deposits in carbonate reservoirs due to its economic efficiency and environmental safety. The article discusses the main mechanisms and processes underlying ion-modified waterflooding and presents the results of laboratory studies conducted on core samples from foreign oil deposits. It includes an analysis of several studies, including contact angle measurements and core flooding experiments on core samples from oil deposits in carbonate reservoirs on the eastern side of the Melekess depression in the Republic of Tatarstan. It is important to note that the Vereyian deposits explored in this article are not a typical example of test objects for ion-modified water injection. This is because they are characterized by a low reservoir temperature of 23 °C, which suggests that the efficiency of the technology would likely be lower compared to studies conducted abroad, where reservoir temperatures were significantly higher. For example, Darvish Sarvestani et al. studied reservoir conditions at 90 °C, Yousef et al. – reservoir temperature of 100 °C, and Austad et al. examined the Ekofisk field at 130 °C and the Volhall field at 90 °C in Norway. However, as several studies have indicated, prolonged contact between rock samples and ion-modified water contributes to significant hydrophilization of the rock surface, as confirmed by contact angle measurements. The contact angle decreases from approximately 138.3° to 53.45° after exposure to ion-modified water. Additionally, the core flooding experiment demonstrated a slight increase in the oil displacement coefficient, reaching 9.2%. These findings suggest the potential for enhanced oil recovery by injecting Smart water into the Vereyian sediments, although further research is required to confirm the underlying mechanism