Optimizing Linezolid: Transforming It into a Selective MAO-B Inhibitor via a Toxicity-to-Activity Optimization Approach.

Linezolid, a widely used oxazolidinone antibiotic, exhibits potent activity against resistant bacterial infections but is associated with serotonergic toxicity, primarily due to its inhibition of monoamine oxidase (MAO). MAOs, consisting of MAO-A and MAO-B isoforms, play crucial roles in neurotransmitter metabolism, with implications for neurodegenerative disorders like Parkinson's and Alzheimer's diseases. This study aims to optimize Linezolid's structure to transform it into a selective MAO-B inhibitor.

Design and Synthesis of Topoisomerases-Histone Deacetylase Dual Targeted Quinoline-Bridged Hydroxamates as Anticancer Agents.

The multifactorial nature of cancer requires treatment that involves simultaneous targeting of associated overexpressed proteins and cell signaling pathways, possibly leading to synergistic effects. Herein, we present a systematic study that involves the simultaneous inhibition of human topoisomerases (hTopos) and histone deacetylases (HDACs) by multitargeted quinoline-bridged hydroxamic acid derivatives. These compounds were rationally designed considering pharmacophoric features and catalytic sites of the cross-talk proteins, synthesized, and assessed for their anticancer potential.

Riparian Soil Heavy Metal Contamination and Pollution Assessment and Management Planning Integrating Multiple Indices, Statistical and Geospatial Approaches.

This research assesses heavy metal contamination within the riparian zone of the Danro River, a tributary of the Ganges River basin in India, particularly impacted by sand mining activities. The study conducted analyses on major and trace elements in soil samples, focusing on those identified as ecologically hazardous by the Water Framework Directive of India. Utilizing a combination of indices (Enrichment Factor, Pollution Load Index, and Index of geo-accumulation) and statistical techniques such as Principal Component Analysis (PCA), the investigation aimed to evaluate contamination severity, ecological risks, and pollution sources.

Organocatalytic [4+2] Benzannulation Between 1,4-Dithiane-Based Enal and Nitroolefins to Access 2-Nitrobiaryls.

A simple method for constructing unsymmetrical 2-nitrobiaryls has been developed between substituted 1,4-dithiine-2-carbaldehyde and nitroolefins under metal-free conditions. To gain the advantage of the HOMO-raising effect of temporary substitutions on in situ generated dienamine intermediate, the present protocol established [4+2] benzannulation of 1,4-dithiane-tethered enals with nitroolefin. Further, easy unmasking of 1,4-dithiine units results in a benzannulation product like that of unsubstituted enals, which are difficult to access.

Targeting the NLRP3 inflammasome as a novel therapeutic target for osteoarthritis.

Osteoarthritis, the most common arthritic condition, is an age-related progressive disease characterized by the loss of cartilage and synovial inflammation in the knees and hips. Development of pain, stiffness, and considerably restricted mobility of the joints are responsible for the production of matrix metalloproteinases and cytokines. Although several treatments are available for the management of this disease condition, they possess limitations at different levels.

Unfolding the Potential of Pyrrole- and Indole-Based Allylidene Hydrazine Carboximidamides as Antimicrobial Agents.

Antimicrobial drug resistance is a significant global health challenge, causing hundreds of thousands of deaths annually and severely impacting healthcare systems worldwide. Several reported antimicrobial compounds have a guanidine motif, as the positive charge on guanidine promotes cell lysis. Therefore, pyrrole- and indole-based allylidene hydrazine carboximidamide derivatives with guanidine motifs are proposed as antimicrobial agents that mimic cationic antimicrobial peptides (CAMPs).

Hot-Exciton Mechanism with Diphenyl Anthracene Core Unit: A Detailed Theoretical Study.

Hot-exciton materials, among all kinds of organic light-emitting diode (OLED) emitters, have better exciton utilization efficiency and efficiency roll-off, making them possible for their practical applications. We studied the photophysical properties of a few hot-exciton molecules based on an anthracene core unit to efficiently harvest all triplet excitons to the lowest excited singlet state. The conversion of triplet exciton to singlet exciton utilizing hRISC can be enhanced due to the 1ππ*←3nπ* transition channel.

Modulation in the charge transfer characteristics of flexible bis-benzimidazole probes: independent sensing mechanisms for Hg and F.

Flexible bis-benzimidazole-based V-shaped amphiphilic probes (1 and 2) that form a fluorescent nanoscopic assembly in aqueous media have been designed. The ion-binding properties of compound 1 are investigated in both polar protic (water) and aprotic (acetonitrile) solvents. In acetonitrile, the compound shows a distinct chromogenic response towards Hg (LOD: 8.

Targeting the epigenome with advanced delivery strategies for epigenetic modulators.

Epigenetics mechanisms play a significant role in human diseases by altering DNA methylation status, chromatin structure, and/or modifying histone proteins. By modulating the epigenetic status, the expression of genes can be regulated without any change in the DNA sequence itself. Epigenetic drugs exhibit promising therapeutic efficacy against several epigenetically originated diseases including several cancers, neurodegenerative diseases, metabolic disorders, cardiovascular disorders, and so forth.

In silico evaluation of bisphosphonates identifies leading candidates for SARS-CoV-2 RdRp inhibition.

The novel coronavirus disease (COVID-19) pandemic has resulted in 777 million confirmed cases and over 7 million deaths worldwide, with insufficient treatment options. Innumerable efforts are being made around the world for faster identification of therapeutic agents to treat the deadly disease. Post Acute Sequelae of SARS-CoV-2 infection or COVID-19 (PASC), also called Long COVID, is still being understood and lacks treatment options as well.

Recent advances in lipid-based nanocarriers for advanced skin cancer therapy.

Skin cancer is prevalent worldwide,surpassing all other forms of cancer and it does not respond effectively to conventional formulations. Treatment of skin cancer further require deeper permeation into the skin. Therefore, researchers are working on different types of nanoformulations for delivering therapeutic agents to the site of action.

Evaluation of Anti-Obesity Potential of Isolated Bioactive Fractions from Justicia Adhatoda Leaves: An In Vitro, In Vivo, and 3T3-L1 cell line Approach Using HPTLC-MS-MSn for Compound Identification.

This study was conducted to investigate the anti-obesity effects of bioactive fractions JAF2 and JAF3 from Justicia adhatoda (JA) in vitro using enzymatic assays, 3T3-L1 cells and in vivo using a monosodium glutamate-high-fat diet (MSG-HFD) model. High-Performance Thin Layer Chromatography coupled with Mass Spectrometry (HPTLC-MS-MSn) was finally utilized to analyze bioactive fractions for the compounds responsible for the activity. In vitro, the anti-obesity effects of JAF2 and JAF3 were assessed in 3T3-L1 adipocytes, revealing that JAF2 significantly reduced lipid and triglyceride levels.

From Plant to Pathway: Molecular Mechanisms of Ruscogenin in Preventing Amyloid-Beta Aggregation through Computational and Experimental Approaches.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline, extracellular amyloid-β (Aβ) plaque accumulation, and intracellular neurofibrillary tangles. Recent efforts to find effective therapies have increased interest in natural compounds with multifaceted effects on AD pathology. This study explores natural compounds for their potential to mitigate AD pathology using molecular docking, ADME screening, and assays, with ruscogenin─a steroidal sapogenin from emerging as a promising candidate.

Engaging a highly fluorescent conjugated polymer network for probing endogenous hypochlorite in macrophage cells: improved sensitivity signal amplification.

We have employed a triazine-based conjugated polymer network (CPN) for the selective detection of hypochlorite in a semi-aqueous environment. CPNs have been widely employed in gas capture, separation, and adsorption, but the fluorescent properties of CPNs possessing extensive π-conjugated systems tend to be unexplored. Herein, we report the photophysical properties of the CPN and investigate its sensing capability towards hypochlorite.

Recent advancements in the therapeutic approaches for Alzheimer's disease treatment: current and future perspective.

Alzheimer's disease (AD) is a complex, incurable neurological condition characterized by cognitive decline, cholinergic neuron reduction, and neuronal loss. Its exact pathology remains uncertain, but multiple treatment hypotheses have emerged. The current treatments, single or combined, alleviate only symptoms and struggle to manage AD due to its multifaceted pathology.

Bare and Ligand-Stabilized Planar Hexacoordinate Boron (phB) in ABeCB (A = P, As, Sb, and Bi) Clusters.

Planar hexacoordination is an extremely uncommon phenomenon for the atoms that belong to the main group. Within this article, we have analyzed the potential energy surfaces (PES) of ABeCB (A = N, P, As, Sb, and Bi) clusters in neutral, monocationic, monoanionic, dicationic, and dianionic states using density functional theory (DFT). Among which PBeCB, PBeCB, AsBeCB, AsBeCB, SbBeCB, and BiBeCB clusters contain a planar hexacoordinate boron (phB) atom in the global minimum energy structures with symmetry.

Electronic Substitution Effect on ESIPT-Driven pH and Amine Sensing: Exploring Mechanism.

It is required to have a more straightforward and easier way to check the quality of food to ensure the safety of the public heaths. The decomposition of meat protein results in ammonia and biogenic amines (BAs).  Here, we have designed and synthesized three luminescent-based probe molecules, which originated from 2-(2-hydroxyphenyl) benzothiazole (HBT) derivatives and showed the excited state-induced proton transfer (ESIPT) phenomenon.

Unveiling structural components of dibenzofuran-based MMP-12 inhibitors: a comparative classification-dependent analysis with molecular docking-based virtual screening and molecular dynamics simulation.

Unlabelled: The implication of matrix metalloproteinase-12 (MMP-12) in various major disorders including cancer, COPD, cardiovascular disorders, and neurological diseases makes it a potential target for drug discovery. Contemplating the significance of MMP-12, a number of MMP-12 inhibitors were designed, synthesized and tested throughout the world but the non-selective nature of most of those molecules can lead to adverse drug interactions. In contradiction, the dibenzofuran (DBF) and dibenzothiophene (DBT) derivatives showed highly potent and selective MMP-12 inhibition.

Evolution of electronic structure and optical properties of naphthalenediimide dithienylvinylene (NDI-TVT) polymer as a function of reduction level: a density functional theory study.

Naphthalenediimide (NDI)-based donor-acceptor co-polymers with tunable electronic, optical, mechanical, and transport properties have shown immense potential as n-type conducting polymers in organic (opto)electronics. During the operation, the polymers undergo reduction at different charged states, which alters their (opto)electronic properties mainly due to the formation of the quasiparticles, polaron/bipolaron. The theoretical study based on quantum mechanical calculations can provide us with a detailed understanding of their (opto)electronic properties, which is missing to a great extent.

Insights into Interlayer Dislocation Augmented Zinc-Ion Storage Kinetics in MoS Nanosheets for Rocking-Chair Zinc-Ion Batteries with Ultralong Cycle-Life.

Increasing attention to sustainability and cost-effectiveness in energy storage sector has catalyzed the rise of rechargeable Zinc-ion batteries (ZIBs). However, finding replacement for limited cycle-life Zn-anode is a major challenge. Molybdenum disulfide (MoS), an insertion-type 2D layered material, has shown promising characteristics as a ZIB anode.

An Azomethine Derivative, 1-(4-nitrophenyl)-N-phenylmethanimine (BCS2) Ameliorated 7,12-dimethylbenz(a)anthracene-induced Mammary Carcinoma through Nrf2-Keap1-HO-1 Pathway.

Aims: The aim of this study is the evaluation of an Azomethine derivative, BCS2, for its antioxidant and anti-tumor activities against mammary carcinoma through the Nrf2- Keap1-HO-1 pathway.

Background: The global prevalence of breast cancer is rising at an alarming rate. The facilitation of abnormal cell proliferation in mammary carcinoma occurs due to the disruption of signaling pathways that balance pro- and antioxidant status, thereby producing oxidative stress that disrupts genomic stability.

Network analysis of differentially expressed genes involved in oral submucous fibrosis and oral squamous cell carcinoma: a comparative approach.

Objective: Oral submucous fibrosis (OSMF) is categorized as an oral potentially malignant disorder (OPMD) with an increased risk of occurrence of oral squamous cell carcinoma (OSCC). In this study, we aimed to identify the hub genes associated with OSMF and OSCC.

Study Design: Using RStudio, a set of differentially expressed genes (DEGs) were identified in (A) OSMF, (B) OSCC, and (C) comparative OSMF-OSCC category, obtained from Gene Expression Omnibus (GEO).

Ni-Co doped TiO catalyst for efficient photocatalytic degradation of Malachite Green under UV and direct sunlight.

In the present study, combustion-synthesized TiO nanoparticles were wet impregnated with Ni, Co, and Ni-Co, respectively. The photocatalytic performance of synthesized catalysts was evaluated against Malachite Green dye. The synthesized materials were characterized for crystallite size, surface morphology, elemental composition, and band gap using X-ray diffraction, scanning electron microscopy, energy dispersive spectroscopy, and ultra-violet diffused reflectance spectroscopy, respectively.

Design, synthesis and in vitro evaluation of primaquine and diaminoquinazoline hybrid molecules against the malaria parasite.

In this study, we built on the known inhibitory potential of diaminoquinazolines (DAQs) against different stages of Plasmodium development and designed a convenient two-step synthesis to combine DAQ with the primaquine (PQ) pharmacophore. The PQ-DAQ hybrids displayed potent in vitro activities in the low nanomolar range (IC50 of 135.20-398.

Structure and dynamics of piperidinium based amino acid ionic liquids: a computational investigation.

Context: There has been growing interest in amino acid ionic liquids because of their low-cost synthesis and superior biodegradability and biocompatibility compared to traditional ionic liquids. In this study, we have investigated the structure and dynamics of three ionic liquids consisting of N-butyl N-methyl piperidinium [Pip] cation with amino acid (lysine [Lys], histidine [His], and arginine [Arg]) anions. The radial distribution functions, the spatial distribution functions, and the coordination numbers have been used to analyze the structure in the bulk phase.