Synthesis, Characterization, and Antimicrobial Activity of Urea-Containing α/β Hybrid Peptides against and Methicillin-Resistant .

The insertion of β-amino acids and replacement of the amide bond with a urea bond in antimicrobial peptide sequences are promising approaches to enhance the antibacterial activity and improve proteolytic stability. Herein, we describe the synthesis, characterization, and antibacterial activity of short αβ cationic hybrid peptides LA-Orn-βAcc-PEA, ; LA-Lys-βAcc-PEA, ; and LA-Arg-βAcc-PEA, in which a C12 lipid chain is conjugated at the N terminus of peptide through urea bonds. Further, we evaluated all the peptides against both and methicillin-resistant (MRSA) and their multidrug resistant (MDR) clinical isolates.

Interrupted borrowing hydrogen strategy enabled aminomethylation and direct cross-dehydrogenative coupling strategy enabled dicarbonylation reactions of imidazo[1,5-]pyridines.

Herein, we disclose the development of novel aminomethylation and dicarbonylation reactions of imidazo[1,5-]pyridines. The developed aminomethylation strategy involves a Pd-catalyzed interrupted borrowing hydrogen strategy by utilizing MeOH as the methylene source. A wide variety of imidazo[1,5-]pyridines and secondary amines were explored for the developed strategy.

Discovery and biological evaluation of nitrofuranyl-pyrazolopyrimidine hybrid conjugates as potent antimicrobial agents targeting and methicillin-resistant .

Nitrofuran and pyrazolopyrimidine-based compounds possess a broad antimicrobial spectrum including Gram-positive and Gram-negative bacteria. In the present work, a series of conjugates of these scaffolds was synthesized and evaluated for antimicrobial activity against and methicillin-resistant (MRSA). Many compounds showed MIC values of ≤2 μg ml, with compound 35 demonstrating excellent activity (MICs: 0.

Targeting InhA in drug-resistant Mycobacterium tuberculosis: potent antimycobacterial activity of diaryl ether dehydrozingerone derivatives.

Tuberculosis (TB) remains a major global threat, with 10 million new cases and 1.5 million deaths each year. In multidrug-resistant tuberculosis (MDR-TB), resistance is most commonly observed against isoniazid (INH) and rifampicin (RIF), the two frontline drugs.

BF·EtO-promoted unconventional reactions of 2-oxoaldehyde: access to 4-amidooxazoles and β-keto amides/sulphonamides.

This study investigates the potential of boron trifluoride etherate (BF·OEt) to trigger unprecedented reactions of 2-oxoaldehydes with nitriles and amides/sulphonamides. In contrast to the mechanism in conventional reactions, the α-carbonyl group in 2-oxoaldehydes induces a cyclization pathway to be followed when reacting with nitriles, yielding 4-amidooxazoles. Additionally, reactions with weak nucleophiles produce β-keto amides/sulphonamides.

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).

Breaking the energy chain: importance of ATP synthase in and its potential as a drug target.

Unveiling novel pathways for drug discovery forms the foundation of a new era in the combat against tuberculosis. The discovery of a novel drug, bedaquiline, targeting mycobacterial ATP synthase highlighted the targetability of the energy metabolism pathway. The significant potency of bedaquiline against heterogeneous population of marks ATP synthase as an important complex of the electron transport chain.

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.

Synthesis and potential anti-inflammatory response of indole and amide derivatives of ursolic acid in LPS-induced RAW 264.7 cells and systemic inflammation mice model: Insights into iNOS, COX2 and NF-κB.

Ursolic acid (3-hydroxy-urs-12-ene-28-oic acid, UA) is a pentacyclic triterpene present in numerous plants, fruits and herbs and exhibits various pharmacological effects. However, UA has limited clinical applicability since it is classified as BCS class IV molecule, characterized by low solubility, low oral bioavailability and low permeability. In the present study, UA was isolated from the biomass marc of Lavandula angustifolia and was structurally modified by an induction of indole ring at the C-3 position and amide group at the C-17 position with the aim to enhance its pharmacological potential.

Corporate genome screening India (CoGsI) identified genetic variants association with T2D in young Indian professionals.

Rising cases of type 2 diabetes (T2D) in India, especially in metropolitan cities is an increasing concern. The individuals that were most affected are young professionals working in the corporate sector. However, the corporate sector has remained the least explored for T2D risk predisposition.

Autophagy inhibition alleviates tumor desmoplasia and improves the efficacy of locally and systemically administered liposomal doxorubicin.

The abnormal physiology of the tumor microenvironment poses a challenge to the drug delivery in the tumor tissues. The dense tumor stroma hinders the movement of nanomedicine through the interstitium and negatively impacts their efficacy. In this study, hydroxychloroquine (HCQ) was investigated for its impact on alleviating the hindrance offered to the nanomedicine by extracellular matrix (ECM) components such as collagen and hyaluronan.

An HPLC-based Assay to Study the Activity of Cyclic Diadenosine Monophosphate (C-di-AMP) Synthase DisA from .

Cyclic diadenosine monophosphate (c-di-AMP) is a recently discovered second messenger that modulates several signal transduction pathways in bacterial and host cells. Besides the bacterial system, c-di-AMP signaling is also connected with the host cytoplasmic surveillance pathways (CSP) that induce type-I IFN responses through STING-mediated pathways. Additionally, c-di-AMP demonstrates potent adjuvant properties, particularly when administered alongside the Bacillus Calmette-Guérin (BCG) vaccine through mucosal routes.

Synthesis of novel spiroisoxazolidino hybrids of alantolactone and isoalantolactone via 1,3 dipolar nitrone cycloaddition and its antimicrobial Evaluation.

Alantolactone and isoalantolactone are two isomeric sesquiterpene lactones that were isolated from Innula recemosa. Here, we are used for the semisynthesis of novel isoxazolidine hybrids of alantolactone and isoalantolactone through a two-step process: nitrone synthesis followed by nitrone 1,3-dipolar cycloaddition. The formation of the cycloadduct was well characterized via modern spectroscopic techniques such as HRMS, H NMR, C NMR, DEPT-90, DEPT-135, and 2D NMR.

Breaking the resistance: integrative approaches with novel therapeutics against Klebsiella pneumoniae.

Klebsiella pneumoniae is a leading cause of anti-microbial resistance in healthcare-associated infections that have posed a severe threat to neonatal and wider community. The escalating crises of antibiotic resistance have compelled researchers to explore an innovative arsenal beginning from natural resources to chemical modifications in order to overcome the ever-increasing resistance issues. The present review highlights the drug discovery efforts with a special focus on cutting-edge strategies in the hunt for potential drug candidates against MDR/XDR Klebsiella pneumoniae.

Structural and functional characterization of genes and enzymes involved in withanolide biosynthesis in Physalis alkekengi L.

Physalis alkekengi L. is recognized as a significant source of various secondary metabolites, particularly C steroidal lactones known as withanolides and physalins, renowned for their therapeutic properties with a rich history in traditional medicine. In this study, we characterized the sequences of key downstream genes (PaFPPS, PaSQS, PaSQE, PaCAS, PaHYD1, and PaDWF5-1) involved in the biosynthesis of withanolides, marking the first characterization of these genes in P.

C-H Functionalization of Imidazo[1,5-]pyridines: A Metal-Free Approach for Methylene Insertion to Access C(sp)-C(sp)-H-C(sp) Bond Formation.

Formaldehyde has been used as a solvent and a source of carbon to insert a methylene group for bridging two imidazo[1,5-]pyridine molecules without using any metal catalysis. This strategy has been extended on other alkyl-, aryl-, and heteroaryl aldehydes as well. This C(sp)-C(sp)-H-C(sp) bond forming reaction proceeds via C(sp)H functionalization of imidazo[1,5-]pyridine and was applied on a wide range of substrates offering moderate to good yields of methylene-bridged/inserted bis-imidazo[1,5-]pyridines.

Miniaturized electrophoresis: An integrated microfluidic cartridge with functionalized hydrogel-assisted LAMP for sample-to-answer analysis of nucleic acid.

Accurate detection of pathogenic nucleic acids is crucial for early diagnosis, effective treatment, and containment of infectious diseases. It facilitates the timely identification of pathogens, aids in monitoring disease outbreaks, and helps prevent the spread of infections within healthcare settings and communities. We developed a multi-layered, paper-based microfluidic and miniaturized electrophoresis system for rapid nucleic acid extraction, separation, amplification, and detection, designed for resource-limited settings.

Structure-Based Virtual Screening and Biological Characterization of Novel BACE-1 and Amyloid-β Aggregation Inhibitors.

Alzheimer's disease (AD) is a complex neurodegenerative disorder having limited treatment options. The beta-site APP cleaving enzyme 1 (BACE-1) is a key target for therapeutic intervention in Alzheimer's disease. To discover new scaffolds for BACE-1 inhibitors, a ChemBridge DIVERSet library of 20,000 small molecules was employed to structure-based virtual screening.

Design and synthesis of betulinic acid-dithiocarbamate conjugates as potential antifungal agents against .

Diverse betulinic acid-dithiocarbamate conjugates were designed and synthesized a two-step reaction at room temperature. Among the fourteen dithiocarbamate analogs of betulinic acid, DTC2 demonstrated the best antifungal activity against , with a minimum inhibitory concentration (MIC) of 4 μg mL, achieving 99% fungicidal activity at the same concentration. These compounds were found to be ineffective against common Gram-negative and Gram-positive pathogens, suggesting their specificity to fungi.

Stereoselective synthesis of 2-deoxy-2-bromo-hexopyrano-β-nucleosides: solvent-free Lewis acid catalysis.

An expedient solvent-free synthesis of 2-deoxy-2-bromo-hexopyrano-β-nucleosides stereo- and regioselectively from protected glycals and unactivated nucleobases using cheaper and easily available reagent systems has been developed. The synthesis is mediated by a Lewis acid and is solvent-free. The substrate scope of the reaction was analysed with ether, ester and silyl-protected glycals as donors and different pyrimidine and purine bases were taken into consideration.

Transcriptome-wide investigation and functional characterization reveal a terpene synthase involved in γ-terpinene biosynthesis in Monarda citriodora.

Monarda citriodora Cerv. ex Lag. is a rich source of industrially important compounds like γ-terpinene, carvacrol, thymol and thymoquinone.