Cold-active enzymes from deep marine psychrophiles: harnessing their potential in enhanced food production and sustainability.

Exploring the untapped potential of deep-sea microorganisms, particularly their cold-active enzymes, or psychrozymes, offers exciting possibilities for revolutionizing various aspects of the food processing industry. This review focuses on these enzymes, derived from the largely unexplored depths of the deep ocean, where microorganisms have developed unique adaptations to extreme conditions. Psychrozymes, as bioactive molecules, hold significant promise for food industry applications.

Dual inhibition of aminoacyl-tRNA synthetase interacting multifunctional protein-2 and α-synuclein by steroid derivative is neuroprotective in Parkinson's model.

Aminoacyl-tRNA synthetase interacting multifunctional protein-2 (AIMP2), a parkin substrate, possesses self-aggregating properties, potentiating α-synuclein aggregation and neurotoxicity in PD. Thus, targeting both α-synuclein and AIMP2 would present an effective treatment for PD pathologies. Herein, we developed small compounds with dual inhibitory activity against AIMP2 and α-synuclein.

Pharmacogenetic Approach to Tramadol Use in the Arab Population.

Tramdol is one of most popular opioids used for postoperative analgesia worldwide. Among Arabic countries, there are reports that its dosage is not appropriate due to cultural background. To provide theoretical background of the proper usage of tramadol, this study analyzed the association between several genetic polymorphisms (CYP2D6/OPRM1) and the effect of tramadol.

Enantioselective Michael addition of 3-hydroxy-2-pyridone to nitroolefins using cinchona-derived bifunctional organocatalysts.

Despite the extensive use of N-heteroarenes in pharmaceuticals and natural products, efficient methods for selective alkylation at the C-4 position of 2-pyridone are scarce. We developed an enantioselective Michael addition of 3-hydroxy-2-pyridone to nitroolefins at the C-4 position using cinchona-derived bifunctional squaramide organocatalysts, achieving up to 95% yield and >99% ee. This selectivity is driven by the bifunctional organocatalysts' hydrogen bonding interactions with 3-hydroxy-2-pyridone and nitroolefins under mild conditions.

In vitro and in vivo investigations on arsenic-induced cartilage degeneration in osteoarthritis.

Heavy metals found in the environment, including arsenic (As) pose significant risks to human health and present a risk factor for osteoarthritis (OA). This study researched the impact of As on cartilage degeneration by focusing on the role of As in causing OA in mice. We employed chemical inhibition and inductively coupled plasma mass spectrometry analyses to identify the effect of As on chondrocytes as well as studying its accumulation in organs after oral administration in mice.

Repurposing and computational design of PARP inhibitors as SARS-CoV-2 inhibitors.

Coronavirus disease 2019 (COVID-19) is a recent pandemic that caused serious global emergency. To identify new and effective therapeutics, we employed a drug repurposing approach. The poly (ADP ribose) polymerase inhibitors were used for this purpose and were repurposed against the main protease (Mpro) target of severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2).

Explicit molecular dynamics simulation studies to discover novel natural compound analogues as inhibitors.

Tuberculosis (TB) in one of the dreadful diseases present globally. This is caused by . dethiobiotin synthetase (DTBS) is an essential enzyme in biotin biosynthesis and is an ideal target to design and develop novel inhibitors.

Pharmacophore-Oriented Identification of Potential Leads as CCR5 Inhibitors to Block HIV Cellular Entry.

Cysteine-cysteine chemokine receptor 5 (CCR5) has been discovered as a co-receptor for cellular entry of human immunodeficiency virus (HIV). Moreover, the role of CCR5 in a variety of cancers and various inflammatory responses was also discovered. Despite the fact that several CCR5 antagonists have been investigated in clinical trials, only Maraviroc has been licensed for use in the treatment of HIV patients.

3D-QSAR-Based Pharmacophore Modeling, Virtual Screening, and Molecular Dynamics Simulations for the Identification of Spleen Tyrosine Kinase Inhibitors.

Spleen tyrosine kinase (SYK) is an essential mediator of immune cell signaling and has been anticipated as a therapeutic target for autoimmune diseases, notably rheumatoid arthritis, allergic rhinitis, asthma, and cancers. Significant attempts have been undertaken in recent years to develop SYK inhibitors; however, limited success has been achieved due to poor pharmacokinetics and adverse effects of inhibitors. The primary goal of this research was to identify potential inhibitors having high affinity, selectivity based on key molecular interactions, and good drug-like properties than the available inhibitor, fostamatinib.

Antimicrobial Resistance, Pathogenic, and Molecular Characterization of from Diarrheal Patients in South Korea.

Diarrheal diseases due to foodborne are the leading cause of illness in humans. Here, we performed pathogenic typing, molecular typing, and antimicrobial susceptibility tests on seventy-five isolates of isolated from stool samples of patients suffering from foodborne diseases in Busan, South Korea. All the isolates were identified as by both biochemical analysis (API 20E system) and matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS).

Recent Advances in Divergent Synthetic Strategies for Indole-Based Natural Product Libraries.

Considering the potential bioactivities of natural product and natural product-like compounds with highly complex and diverse structures, the screening of collections and small-molecule libraries for high-throughput screening (HTS) and high-content screening (HCS) has emerged as a powerful tool in the development of novel therapeutic agents. Herein, we review the recent advances in divergent synthetic approaches such as complexity-to-diversity (Ctd) and biomimetic strategies for the generation of structurally complex and diverse indole-based natural product and natural product-like small-molecule libraries.

Recent Achievements in Total Synthesis for Integral Structural Revisions of Marine Natural Products.

A great effort to discover new therapeutic ingredients is often initiated through the discovery of the existence of novel marine natural products. Since substances produced by the marine environment might be structurally more complex and unique than terrestrial natural products, there have been cases of misassignments of their structures despite the availability of modern spectroscopic and computational chemistry techniques. When it comes to refutation to erroneously or tentatively proposed structures empirical preparations through organic chemical synthesis has the greatest contribution along with close and sophiscated inspection of spectroscopic data.

Computational Simulations Highlight the IL2Rα Binding Potential of Polyphenol Stilbenes from Fenugreek.

Widely used in global households, fenugreek is well known for its culinary and medicinal uses. The various reported medicinal properties of fenugreek are by virtue of the different natural phytochemicals present in it. Regarded as a promising target, interleukin 2 receptor subunit alpha (IL2Rα) has been shown to influence immune responses.

Asymmetric Phase-Transfer Catalytic aza-Michael Addition to Cyclic Enone: Highly Enantioselective and Diastereoselective Synthesis of Cyclic 1,3-Aminoalcohols.

The highly enantioselective aza-Michael reaction of -butyl β-naphthylmethoxycarbamate to cyclic enones has been accomplished by using a new alkaloid derived C(9)-urea ammonium catalyst under phase-transfer catalysis conditions with up to 98% ee at 0 °C. The resulting aza-Michael adducts can be converted to versatile intermediates by selective deprotection and the cyclic 1,3-aminoalcohols by diastereoselective reduction with up to 32:1, which have been widely used as important pharmacophores in pharmaceutical development.

Membrane vesicles from antibiotic-resistant Staphylococcus aureus transfer antibiotic-resistance to antibiotic-susceptible Escherichia coli.

Aim: Bacteria naturally produce membrane vesicles (MVs), which have been shown to contribute to the spread of multi-drug resistant bacteria (MDR) by delivering antibiotic-resistant substances to antibiotic-susceptible bacteria. Here, we aim to show that MVs from Gram-positive bacteria are capable of transferring β-lactam antibiotic-resistant substances to antibiotic-sensitive Gram-negative bacteria.

Materials And Methods: MVs were collected from a methicillin-resistant strain of Staphylococcus aureus (MRSA) and vesicle-mediated fusion with antimicrobial-sensitive Escherichia coli (RC85).

Recent Advances in the Synthesis of Ibuprofen and Naproxen.

Herein, we review the recent progress in the synthesis of representative nonsteroidal anti-inflammatory drugs (NSAIDs), ibuprofen and naproxen. Although these drugs were discovered over 50 years ago, novel practical and asymmetric approaches are still being developed for their synthesis. In addition, this endeavor has enabled access to more potent and selective derivatives from the key frameworks of ibuprofen and naproxen.

Synthesis and biological activity of selenopsammaplin A and its analogues as antitumor agents with DOT1L inhibitory activity.

Disruptor of telomeric silencing-1 like (DOT1L) is a histone H3 methyltransferase which specifically catalyzes the methylation of histone H3 lysine-79 residue. Recent findings demonstrate that DOT1L is abnormally overexpressed and the upregulated DOT1L evokes the proliferation and metastasis in human breast cancer cells. Therefore, the DOT1L inhibitor is considered a promising strategy to treat breast cancers.

Enantioselective Total Synthesis of Alkaloids: (+)-Nitramine, (+)-Isonitramine, (-)-Isonitramine, and (-)-Sibirine via Asymmetric Phase-Transfer Catalytic α-Allylations of α-Carboxylactams.

Many optically active 2-azaspirocyclic structures have frequently been found in biologically active natural products. In particular, alkaloids, (+)-nitramine, (+)-isonitramine, (-)-isonitramine, and (-)-sibirine, have stereogenicity on their quaternary carbon of the 2-azaspiro[5,5]undecane-7-ol structure. To synthesize alkaloids, we developed a new enantioselective synthetic method for chiral α-quaternary lactams via the α-alkylation of α--butoxycarbonyl lactams.

Enantioselective Synthesis of (+)-Coerulescine by a Phase-Transfer Catalytic Allylation of Diphenylmethyl -Butyl α-(2-Nitrophenyl)Malonate.

A 7-step enantioselective synthetic method for preparing (S)(+)-coerulescine is reported through the use of diphenylmethyl tert-butyl α-(2-nitrophenyl)malonate (16% overall yield, >99% ee). Allylation is the key step under phase-transfer catalytic conditions (86% ee). This synthetic method can be used as a practical route for the synthesis of various derivatives of (S)(+)-coerulescine for analyzing its structure-activity relationships against its biological activities.

Design and Synthesis of Small Molecules as Potent Sortase A Inhibitors.

The widespread and uncontrollable emergence of antibiotic-resistant bacteria, especially methicillin-resistant , has promoted a wave of efforts to discover a new generation of antibiotics that prevent or treat bacterial infections neither as bactericides nor bacteriostats. Due to its crucial role in virulence and its nonessentiality in bacterial survival, sortase A has been considered as a great target for new antibiotics. Sortase A inhibitors have emerged as promising alternative antivirulence agents against bacteria.

Mobility Models Based on Forward Current-Voltage Characteristics of P-type Pseudo-Vertical Diamond Schottky Barrier Diodes.

Compared with silicon and silicon carbide, diamond has superior material parameters and is therefore suitable for power switching devices. Numerical simulation is important for predicting the electric characteristics of diamond devices before fabrication. Here, we present numerical simulations of p-type diamond pseudo-vertical Schottky barrier diodes using various mobility models.

High-Efficiency Diphenylpyrimidine Derivatives Blue Thermally Activated Delayed Fluorescence Organic Light-Emitting Diodes.

Organic light-emitting diodes with thermally activated delayed fluorescence emitter have been developed with highly twisted donor-acceptor configurations and color-pure blue emitters. Synthesized 4-(4-(4,6-diphenylpyrimidin-2-yl)phenyl)-10H-spiro[acridine-9,9'-fluorene] (4,6-PhPMAF) doped device with spiroacridine as a donor unit and diphenylpyrimidine as acceptor exhibits the device characteristics such as the luminescence, external quantum efficiencies, current efficiencies, and power efficiencies corresponding to 213 cd/m, 2.95%, 3.

Enhancement of cortisol measurement sensitivity by laser illumination for AlGaN/GaN transistor biosensor.

In this study, high electron mobility transistor (HEMT) device was used as an immuno biosensor to measure concentration of a stress hormone, cortisol, by using selective binding on cortisol monoclonal antibody (c-Mab). Also, the HEMT sensor was enhanced in its sensitivity through light illumination to generate photocurrent. The optical pumping could assist the biosensor to discriminate more detailed change, which could result in an increment of limit of detection (LOD) to 1.

The Importance of Porins and β-Lactamase in Outer Membrane Vesicles on the Hydrolysis of β-Lactam Antibiotics.

Gram-negative bacteria have an outer membrane inhibiting the entry of antibiotics. Porins, found within the outer membrane, are involved in regulating the permeability of β-lactam antibiotics. β-lactamases are enzymes that are able to inactivate the antibacterial properties of β-lactam antibiotics.