Synthesis of 1,3-diaryl substituted pyrazole-based imidazo[1,2-a]pyridine carboxamides and evaluation of their antitubercular activity.

The rise of drug-resistant tuberculosis (TB) has created an urgent need to discover and develop new anti-mycobacterial agents. Herein, we report the synthesis and evaluation of a library of 1,3-diaryl substituted pyrazole-based imidazo[1,2-a]pyridine carboxamides as promising anti-TB agents. In preliminary screening, 10 out of 26 compounds displayed potent in vitro inhibition against Mtb H37Rv with a MIC value of 0.

Value Addition to Citrus maxima Peels: Extraction and Modification of Naringenin into Hydrazones Derivatives for Anti-Breast Cancer and Osteogenic Activity via In Vitro and In Silico Studies.

This study investigates the value addition of Citrus maxima fruit peels by extracting Naringenin and chemically modifying it into hydrazone derivatives to enhance its anti-cancer and anti-osteoporotic potential. The compounds (2a-f) were synthesised using simple and efficient chemistry. Their pharmacokinetic properties, molecular docking and simulations were evaluated against key hormonal targets, EGFR, ERα, ERβ, HER2 and PR.

Curcumin monoglucuronide protects cartilage from progressive degeneration by blocking MMP-13.

Collagenases (MMP-1, MMP-8, and MMP-13) play significant roles in the pathophysiology of osteoarthritis. Among these proteins, MMP-13 and MMP-8 are known for their catabolic roles in the degradation of the articular cartilage matrix. Using computational studies, we had previously observed that a metabolite of curcumin, Curcumin monoglucuronide (CMG), binds to MMPs involved in cartilage matrix destruction.

Amphiphilicity to α/γ Hybrid Foldamers through Post-Modification at Multiple Sites: Antimicrobial Design and Structure-Function Relationship.

Antimicrobial drug design is an active area of research. Drug resistance in microorganisms to conventional antibiotics imposes a huge burden on the healthcare and economy worldwide. Understanding the structural parameters controlling the antimicrobial activity enables researchers to develop effective antimicrobial agents.

Regioselective construction of pyrido[1,2,3-]quinoxaline-2,5-diones through acid-mediated post-Ugi rearrangements.

We report a robust method for preparing uniquely functionalized pyrido[1,2,3-]quinoxaline-2,5-diones from alkynamide-containing Ugi adducts under acidic conditions. This single-step process proceeds through spirocyclization of Ugi adducts followed by intramolecular condensation and ring expansion in a highly regioselective manner. Mechanistic studies and DFT calculations were performed to establish the reaction path and possible intermediates.

Purification and Characterization of Antimicrobial Peptide from an Epilithic Bacterium Streptomyces sp. AL50 with Activity Against Biofilm Forming Coagulase-Negative Staphylococci.

Antimicrobial peptide (AMP) is increasingly recognized as a promising new avenue in addressing the challenge of antibiotic resistance, offering a notable alternative to traditional antibiotic molecules. The current research focuses on extracting and characterizing AMP named as AMP1 from epilithic bacterial isolate Streptomyces sp. AL50, an area that has so far remained underexplored.

HFIP-Mediated Spiro-annulation of Bicyclo[1.1.0]butanes with α-Halo Hydroxamates: Access to Functionalized Spirocyclobutenes.

Bicyclo[1.1.0]butanes (BCBs) are activated using photocatalysts, Lewis and Brønsted acids, transition metal catalysts, and more recently hexafluoroisopropanol (HFIP).

Bioinspired Plasmonic Glyconanosensors for Onsite Optical Detection of Uropathogenic in Urine Samples.

Urinary tract infections (UTIs) are known to impact the lives of 150 million people each year and largely influence the global index of infection. The high rate of incidence of UTIs results in high rates of morbidity and mortality worldwide. The limitation in currently available techniques for the early diagnosis of UTIs is the main reason behind its severity.

Nucleobase self-assembly: aggregation, morphological characterization, and toxicity analysis.

This study expands the platform for amyloidogenic building blocks, such as nucleobases, and their self-assembly. Here, we examine the self-assembly profile of nucleobases such as guanine, cytosine, and thymine and determine that these nucleobases, while aged, produce small globules which gradually transform into fibrillar assemblies. Notably, the amyloid-like fibrillation in adenine and uracil has already been reported; hence, it was imperative to understand the amyloidogenic propensity in these unexplored nucleobases.

1,3,4-thiadiazole derivatives as PI3Ks inhibitor: design, in silico studies, synthesis, characterization, and antimicrobial evaluation.

Since PI3Ks are targeted by a variety of bacterial pathogens, they represent a promising target for host-directed immune therapy and may be beneficial in managing persistent bacterial infections. In the present study, computational studies of 5-(pyridin-4-yl)-1,3,4-thiadiazol-2-amine derivatives for phosphoinositide-3-kinases (PI3Ks) inhibitors were carried out using dock scores, Glide scores, and the MMGBSA dG method, with comparison to standard drugs (ofloxacin and fluconazole). A series of 5-(pyridin-4-yl)-1,3,4-thiadiazol-2-amine derivatives (D1-D17) were synthesized and evaluated for their in vitro antimicrobial activity against both gram-positive and gram-negative bacterial strains, as well as fungal strains, using the tube dilution method.

Multiple myeloma: Insights into underlying mechanisms, advances in diagnostic and therapeutic modalities.

Multiple myeloma (MM) is characterized by malignant proliferation and accumulation of terminally differentiated antibody-producing plasma cells in bone marrow. The underlying genetic causes of MM are highly complex, involving the loss of function in a myriad of crucial genes, especially those involved in DNA replication fidelity and repair. The important genetic events underscoring MM mutagenesis entail large-scale chromosomal aberrations, localized genetic changes, defective DNA repair mechanisms, point mutation, and mutagenic activity of enzymes such as activation-induced deaminase (AID) and apolipoprotein B mRNA editing enzyme, and catalytic polypeptide (APOBEC).

Sca-1 expression depicts pro-inflammatory murine neutrophils under steady-state and pathological conditions.

Neutrophils play a critical role in various pathophysiological conditions. However, their therapeutic targeting has been challenging due to the associated risk of infections. Therefore, identifying disease-associated neutrophil populations is essential for targeted strategies.

Designing of Peptide Vaccine by Investigating Monkeypox Virus Membrane Glycoprotein: An Integrated In Silico and Immunoinformatics Approach.

Background: In 2022, the World Health Organisation (WHO) announced new cases of the developing Monkeypox Virus (MPXV), a zoonotic orthopoxvirus viral infection that mimics smallpox signs. Despite the ongoing infection, no proper medication is available to completely overcome this infection.

Aim: The study aims to construct a multi-epitope vaccine targeting Monkeypox Virus (MPXV) membrane glycoprotein to provoke robust immune responses.

U50 488H KOR agonist reduces cartilage degradation, chondrocyte hypertrophy and bone loss in osteoarthritis.

Osteoarthritis is a chronic joint disease-causing significant pain and discomfort especially in the aging population. It is characterized by inflammation, extracellular matrix degradation, chondrocyte apoptosis, hypertrophy and subchondral bone degeneration. In this study, we explored the disease modifying activity of Kappa Opioid Receptor (KOR) agonist U50 488H in in-vitro and in-vivo model of osteoarthritis.

CYP2E1 overexpression in hepatocellular carcinoma modulates tumor invasion and migration via Wnt/β-catenin signaling pathway.

Hepatocellular carcinoma (HCC) is the primary cause of cancer-related mortality in the world. Cytochrome P450 2E1 (CYP2E1) plays a key role in metabolizing xenobiotics and toxic substances. The attempts to target CYP2E1 with inhibitors have yielded limited success in cancer treatment.

Impact of IMT-P8 on the Efficacy of Conventional Antibiotics for the Treatment of Drug-Resistant and Intracellular .

Addressing the issue of antimicrobial resistance is of the utmost importance on a global scale. We are in dire need of innovative methods and alternatives to new antibiotic discovery in order to address the growing problem of antimicrobial resistance. In this study, we investigated the efficacy of cell-penetrating peptide (IMT-P8) as an adjuvant to enhance the activity of conventional antibiotics against multidrug-resistant and intracellular in vitro and in vivo IMT-P8 potentiates various antibiotics belonging to different classes.

Exploration of pyrazole-based pyridine-4-carbohydrazide derivatives as drug-resistant agents: design, synthesis, biological evaluation, and studies.

Background: Development of new effective drugs against multidrug resistant is the need of the hour to combat tuberculosis (TB) disease.

Materials And Methods: Pyridine-4-carbohydrazide and substituted pyrazole aldehydes were used to synthesize target molecules (6a-r) which were evaluated against HRv and drug-resistant TB strains. Time kill kinetics assay was performed to check bactericidal/bacteriostatic effect, molecular docking, dynamics simulation over 100 ns was performed against enoyl acyl carrier protein reductase (InhA) along with QSAR, ADMET profile prediction.

Synthesis and evaluation of lactam and maleimide derivatives of 16-hydroxycleroda-3, 13 (14) Z-dien-15, 16-olide from Polyalthia longifolia as potential anticancer agents.

Diterpenes are plant secondary metabolites with diverse bioactivities, yet their anticancer potential remains underexplored. Here, we report the design and synthesis of thirty-nine novel derivatives of clerodane diterpene 1, isolated from Polyalthia longifolia, including twenty lactam and nineteen maleimide analogs. All compounds were screened at 10 μM against colon (DLD-1, HCT116, HT-29) and breast (MCF-7, MDA-MB-231, 4T1) cancer cell lines.

PEGylated MXene@AgNP nanocomposite for targeted release of docetaxel to breast carcinoma.

Aim: MXene pertains to the family of two-dimensional materials with excellent surface area, biocompatibility, and many possibilities for surface functionalization. Owing to this, a multifunctional MXene nanocomposite was developed for targeted drug delivery at tumor site as current treatment regimens show increased adverse effects and limited selectivity.

Method: MAX phase titanium aluminum carbide (TiAlC) was synthesized, which serves as the precursor for the production of TiCT MXene.

In-silico guided identification and studies of potential FFAR4 agonists for type 2 diabetes mellitus therapy.

Background: The activation of free fatty acid receptor 4 (FFAR4) enhances insulin sensitivity and glucose uptake while mitigating inflammation. It is a promising therapeutic approach for managing type 2 diabetes mellitus (T2DM).

Research Design And Methods: Structure and Ligand-based screening approaches were employed to evaluate 1.

Harnessing a deep-sea EAL-domain enzyme for quorum quenching and biofilm control in food pipelines.

This study explores the potential of quorum-quenching (QQ) enzymes from deep-sea bacteria to disrupt bacterial communication and biofilm formation. Among 21 psychrophilic marine isolates, Vibrio sp. strain SAT06 showed broad-spectrum QQ activity by degrading both short (C-HSL) and long-chain (3-O-C-HSL) acyl homoserine lactones.

Augmentation of Antimicrobial Activity of Spiniferin by Introducing an Arginine Residue Toward Its Amino Terminus: A Possible Role of Cation-π Interaction.

Spiniferin is a 13-mer scorpion-origin antimicrobial peptide having poor antimicrobial activity. To augment Spiniferin's antimicrobial activity, we enhanced its net positive charge by replacing a glutamic acid residue with an arginine residue toward its amino terminus. We envisaged that a cation-π interaction could be introduced between this arginine residue and the tryptophan residue located near the middle of Spiniferin.

Emerging Trends in cervical cancer Treatment: Transitioning from traditional to innovative delivery strategies.

Cervical cancer (CC) remains the second most common cause of cancer-related deaths among women in the United States, following breast cancer. As per American Cancer Society reports, with approximately 4,320 deaths expected annually, it continues to pose a significant threat to global public health. The highest prevalence of CC has been reported in low to middle-income nations in Asia, Africa, and Latin America, where screening and treatment are scarce.