Discovery of Non-Peptide GLP-1 Positive Allosteric Modulators from Natural Products: Virtual Screening, Molecular Dynamics, ADMET Profiling, Repurposing, and Chemical Scaffolds Identification.

Glucagon-like peptide-1 (GLP-1) receptor is currently one of the most explored targets exploited for the management of diabetes and obesity, with many aspects of its mechanisms behind cardiovascular protection yet to be fully elucidated. Research dedicated towards the development of oral GLP-1 therapy and non-peptide ligands with broader clinical applications is crucial towards unveiling the full therapeutic capacity of this potent class of medicines. This study describes the virtual screening of a natural product database consisting of 695,133 compounds for positive GLP-1 allosteric modulation.

Gallic Acid: A Potent Metabolite Targeting Shikimate Kinase in .

is a highly multidrug-resistant pathogen resistant to almost all classes of antibiotics; new therapeutic strategies against this infectious agent are urgently needed. Shikimate kinase is an enzyme belonging to the shikimate pathway and has become a potential target for drug development. This work describes the search for Food and Drug Administration (FDA)-approved drugs and natural compounds, including gallic acid, that could be repurposed as selective shikimate kinase inhibitors by integrated computational and experimental approaches.

Drug Repurposing for Cancer Treatment: A Comprehensive Review.

Cancer ranks among the primary contributors to global mortality. In 2022, the global incidence of new cancer cases reached about 20 million, while the number of cancer-related fatalities reached 9.7 million.

Synthesis and antiproliferative activity of 2-oxo-3-phenylquinoxaline derivatives and related compounds against colon cancer.

We have designed 17 new 2-oxo-3-phenylquinoxalines the chemoselective Michael reaction of 3-phenylquinoxalin-2(1)-one with acrylic acid derivatives. The ester, ethyl 3-(2-oxo-3-phenylquinoxalin-1(2)-yl)propanoate, was reacted with hydroxylamine and hydrazine to produce -hydroxy-3-(2-oxo-3-phenylquinoxalin-1(2)-yl)propanamide and hydrazide, respectively. Further modifications were made through reactions with isothiocyanates and azide coupling with amines, yielding thiosemicarbazides and -alkyl derivatives.

Exploring Marine-Derived Compounds: In Silico Discovery of Selective Ketohexokinase (KHK) Inhibitors for Metabolic Disease Therapy.

The increasing prevalence of metabolic diseases, including nonalcoholic fatty liver disease (NAFLD), obesity, and type 2 diabetes, poses significant global health challenges. Ketohexokinase (KHK), an enzyme crucial in fructose metabolism, is a potential therapeutic target due to its role in these conditions. This study focused on the discovery of selective KHK inhibitors using in silico methods.

Spectrofluorometric determination of futibatinib in human plasma and pharmaceutical formulations.

Futibatinib is a powerful inhibitor of fibroblast growth factor receptors that impedes its phosphorylation and subsequently leading to a reduction in in cell viability across various cell lines. Futibatinib was approved for initial use as an effective treatment for several diseases, including non-small cell lung cancer and breast cancer. Herein, a novel selective fluorescence probe was created for futibatinib quantification in various matrices, including pharmaceutical formulation and human plasma.

Synthesis of novel phthalazine-based derivatives with potent cytotoxicity against HCT-116 cells through apoptosis and VEGFR2 inhibition.

The parent ethyl 3-(4-benzyl-1-oxophthalazin-2(1)-yl) propanoate (3) has 25 compounds. Their respective mono, dipeptides and hydrazones derivatives were produced by chemoselective -alkylation addition reaction of 4-benzylphthalazin-1(2)-one (2) with ethyl acrylate and anhydrous potassium carbonate to give ethyl 3-(4-benzyl-1-oxophthalazin-2(1)-yl) propanoate (3). The ester 3 was hydrazinolyzed to give the corresponding hydrazide 3-(4-benzyl-1-oxophthalazin-2(1)-yl) propanehydrazide (5), then azide 6 coupled with amino acid ester hydrochloride and/or amines to afford several parent esters 8a-c, then a series of hydrazinolyzed reactions occurred to give corresponding hydrazides 9a-c.

Revolutionizing Treatment Strategies for Autoimmune and Inflammatory Disorders: The Impact of Dipeptidyl-Peptidase 4 Inhibitors.

DPP4 (Dipeptidyl-peptidase 4) a versatile protease, emerges as a prominent player in soluble and membrane-bound forms. Its heightened expression has been intimately linked to the initiation and severity of diverse autoimmune diseases, spanning rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis (SSc), inflammatory bowel disease, autoimmune diabetes, and even SARS-CoV-2 infection. Operating as a co-stimulator of T cell activity, DPP4 propels T cell proliferation by binding adenosine deaminase (ADA), thereby augmenting the breakdown of adenosine-an influential inhibitor of T cell proliferation.

Investigation of Simultaneous and Sequential Cooperative Homotropic Inhibitor Binding to the Catalytic Chamber of SARS-CoV-2 RNA-dependent RNA Polymerase (RdRp).

In our previous report, the unique architecture of the catalytic chamber of the SARS-CoV-2 RNA-dependent RNA polymerase (RdRp), which harbours two distinctive binding sites, was fully characterized at molecular level. The significant differences in the two binding sites BS1 and BS2 in terms of binding pockets motif, as well as the preferential affinities of eight anti-viral drugs to each of the two binding sites were described. Recent Cryogenic Electron Microscopy (Cryo-EM) studies on the RdRp revealed that two suramin molecules, a SARS-CoV-2 inhibitor, bind to RdRp in two different sites with distinctive interaction landscape.

Application of a nucleophilic substitution reaction for spectrofluorimetric determination of aripiprazole in pharmaceutical dosage form and plasma matrix; greenness assessment.

Aripiprazole is an antipsychotic medicine used to treat a variety of mental disorders, including irritability linked with autism disorder in children. Herein, a green and highly sensitive spectrofluorimetric method was developed for the determination of aripiprazole in pharmaceutical dosage form and plasma matrix. The method based on the formation of a fluorescent adduct from the nucleophilic substitution reaction of 4-chloro-7-nitrobenzo-2-oxa-1,3-diazole (NBD-chloride) with aripiprazole, which can be detected at 542 nm following excitation at 481 nm.

Guava-fruit based synthesis of carbon quantum dots for spectrofluorometric quantitative analysis of risperidone in spiked human plasma and pharmaceutical dosage forms.

Autism is one of the most pressing issues facing the international community in recent years, particularly in Middle Eastern countries. Risperidone is a selective serotonin type 2 and dopamine type 2 receptor antagonist. It is the most administered antipsychotic medication in children with autism-related behavioral disorders.

Frankincense oil-loaded nanoemulsion formulation of paclitaxel and erucin: A synergistic combination for ameliorating drug resistance in breast cancer: and study.

Nanoformulation-based combinational drug delivery systems are well known to overcome drug resistance in cancer management. Among them, nanoemulsions are well-known and thermodynamically stable drug delivery systems suitable for carrying hydrophobic drugs and phytoconstituents to tackle drug-resistant cancers. In the present study, we have investigated the effect of paclitaxel in combination with erucin (natural isothiocyanate isolated from the seeds of ) loaded in the frankincense oil-based nanoemulsion formulation.

A multifaceted approach to identify non-specific enzyme inhibition: Application to Mycobacterium tuberculosis shikimate kinase.

Single dose high-throughput screening (HTS) followed by dose-response evaluations is a common strategy for the identification of initial hits for further development. Early identification and exclusion of false positives is a cost-saving and essential step in early drug discovery. One of the mechanisms of false positive compounds is the formation of aggregates in assays.