The gut microbiome plays a crucial role in renal diseases, influencing conditions such as renal cell carcinoma (RCC), acute kidney injuries, and diabetic nephropathy. Recent studies highlight the association between gut microbial metabolites (GMM) and RCC progression. This study employs a computational network pharmacology framework to explore the mechanistic action of gut microbiota-derived metabolites

Predicting molecular and quantum material properties, especially the band gap, is crucial for accelerating discoveries in drug design and material science. Although graph neural networks and probabilistic encoders are well established in molecular data analysis, their targeted integration and application for band-gap prediction remain an active research area. This paper introduces QMGBP-DL, a deep

Obesity, diabetes, and cardiovascular diseases are major health concerns worldwide. In recent times, research has focused on identifying food-derived molecules and their relationship with metabolic diseases. A study was conducted to establish a process for characterizing the biological targets of capsaicinoids found in chili peppers. Capsaicinoids are a group of compounds including Capsaicin, Dihydrocapsaicin

In humans, rheumatoid arthritis (RA) is a deadly autoimmune disease that affects bone health. Although the specific etiology of RA is unknown, scientific evidence suggests that smoking, genetic abnormalities, and environmental factors may all contribute to the disease’s progression. We employed protein–protein interaction (PPI) networking analysis to identify a possible therapeutic target for RA. The

Among the foremost goals for organic chemists is to discover novel approaches for the synthesis of a particular heterocyclic and its design. Our approach focused on the vital precursor 4-acetyl-3-phenylisoxazol-5(4H)-one 3, as this molecule has an endocyclic carbonyl function in position 5 adjacent to the substituted acetyl function at site 4. Therefore, compound 3 was a crucial component of many types

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the leading cause of chronic liver disease globally. A low-carbohydrate diet (LCD) offers benefits to MASLD patients, albeit its exact mechanism is not fully understood. Using public liver transcriptome data from MASLD patients before/after LCD intervention, we applied differential expression analysis and machine learning to identify

Due to the blood–brain barrier (BBB), DNA topoisomerase I (Topo I) inhibitors often cause dose-limiting toxicity in glioblastoma (GBM) treatment. Therefore, developing low-toxicity Topo I inhibitors with enhanced BBB permeability holds a significant promise for improving GBM treatment outcomes. In this study, structure-based virtual screening methods combined with biological evaluations successfully

Poly (ADP-ribose) polymerase-1 (PARP-1) is a key enzyme in the base excision repair pathway, crucial for maintaining genomic stability by repairing DNA breaks. In cancers with mutations in DNA repair genes, such as BRCA1 and BRCA2, PARP-1 activity becomes essential for tumor cell survival, making it a promising target for therapeutic intervention. This study employs QSAR modeling, virtual screening

A series of 2-aminothiazole derivatives (3A1–3A30) containing 9-alkyl purine moiety were designed and synthesized to explore novel antibacterial agents with unique structures and potent antibacterial activity. The structures of target compounds were characterized using 1H NMR, 13C NMR, and HRMS techniques. The structure of compound 3A12 was further elucidated through single crystal X-ray diffraction

Different species of mosquitoes are responsible for transmitting infectious diseases such as chikungunya, dengue, Japanese encephalitis, lymphatic filariasis, rift valley fever, west nile fever, yellow fever, zika virus, and malaria. Particularly, malaria infection is endemic in sub-Saharan Africa region, and female anopheles mosquitoes is responsible for the transmission of the parasite causing the

Ball milling has emerged as a powerful and sustainable technique for the synthesis of heterocyclic compounds, offering significant advantages over conventional methods. This review explores recent advancements in the application of ball milling for environmentally friendly synthesis, highlighting its role in accelerating reaction times, enhancing yields, and minimizing solvent usage. Various studies

Photodynamic therapy (PDT) has received much attention in cancer treatment because of its low toxicity and side effects. In this study, we successfully synthesized 14 novel porphyrin-formononetin derivatives. In reactive oxygen species detection experiments, the target compounds 4a–6d caused a significant decrease in the fluorescence intensity of DPBF compared with the porphyrin parent and formononetin

The overexpression of the Aldehyde Dehydrogenases 1A subfamily (ALDH1As) in various diseases, particularly in cancer, has made it an important target for therapeutic applications. Interestingly, the 1A1 isoenzyme plays a role in tumor initiation and progression, being identified as a biomarker for cancer stem cells. However, although promising, current ALDH1A1 inhibitors suffer from a lack of isoform

Organoboron compounds play a pivotal role in diverse scientific disciplines, including chemistry, materials science, energy research, and medicinal chemistry. In recent years, research efforts have predominantly focused on 1,2-metallate migrations of tetracoordinate boronate complexes, while remote migrations, particularly 1,n-metallate migrations (n > 2), remain challenging due to their inherent complexity

The process of various virus entry into host cells, including SARS-CoV-2, is mediated by clathrin-mediated endocytosis (CME). AP-2 plays a crucial role in this process by recognizing membrane receptors and binding with clathrin, facilitating the formation of clathrin-coated vesicles and promoting CME. AAK1 catalyzes the phosphorylation of AP2M1 subunit at Thr156. Therefore, suppressing AAK1 activity

Farnesoid X receptor (FXR) is a key regulator of bile acid, lipid, and glucose homeostasis, making it a promising target for treating metabolic diseases. FXR antagonists have shown therapeutic potential in cholestasis, metabolic disorders, and certain cancers, while clinically approved FXR antagonists remain unavailable and underrepresented in current treatment strategies. To address this, we developed

Glycogen synthase kinase-3 beta, GSK-3β, is one of the most common targets for cancer treatment. Inhibiting the biological activity of the enzyme can lead to the prevention of cancer development. Especially, estimating a new inhibitor for preventing GSK-3β by using natural compounds is of great interest. In this context, the marine compounds were investigated for their ligand-binding affinity to GSK-3β

The TIGIT-PVR signalling pathway is a key mechanism of tumour immune evasion, making it an attractive target for cancer immunotherapy. Despite the recent advances in anti-TIGIT antibodies, monoclonal antibody-based therapeutics present significant challenges because of their immunogenicity and immune-related side effects. This study presents a new path involving natural compounds as potential small

An ongoing escalation in malaria cases is a critical global health issue and also a leading source of increased mortality rates. Infected mosquitos spread the Plasmodium parasite-based disease,. Recent advancements in antimalarial drug discovery have focused on developing novel molecules with unique mechanisms of action to combat this growing resistance. This review focuses on the latest findings in

Antiviral peptides (AVPs) represent a novel and promising therapeutic alternative to conventional antiviral treatments, due to their broad-spectrum activity, high specificity, and low toxicity. The emergence of zoonotic viruses such as Zika, Ebola, and SARS-CoV-2 have accelerated AVP research, driven by advancements in data availability and artificial intelligence (AI). This review focuses on the development

A series of novel 2-trifluoromethyl-4-aminoquinazoline derivatives were designed and synthesized, and their antitumor activities were evaluated. Among them, several target compounds exhibited nanomolar inhibitory activities against K562 and LNCaP. Meanwhile, the results of in vitro and in vivo activity evaluation showed that compound 9 had the significant selective anticancer activity and the lower

Given the prevalence and significance of flavanones, we present a regio- and chemoselective approach for the synthesis of flavanone isosteres. This method is facilitated by the synergistic effects of hydrogen bonding and solvent interactions. Notably, this novel multicomponent reaction employs commercially available starting materials, operates without the need for catalysts, and achieves high levels

Staphylococcus aureus is an opportunistic microorganism which can cause minor skin infections and also serious diseases, and its increasing antibiotic resistance necessitates further discovery of new targets and inhibitors for antibacterials. The transmembrane protein LcpASA that plays an essential role in the synthesis of cell wall in S. aureus has been identified as a potential drug target. In this

Breast cancer is one of the leading reasons of mortality due to cancer globally. Estrogen receptor-positive (ER +) breast cancer being a significant subtype. The therapeutic potential of Vitamin D3 in cancer treatment has gained attention due to its ability to modulate key molecular targets and signaling pathways. This study investigates the anticancer mechanisms of Vitamin D3 in MCF-7 breast cancer

Cancer cells can hijack receptor-interacting protein kinase 1 (RIPK1) and exploit its scaffolding function to orchestrate pro-survival signaling and fuel immunosuppressive program. Accordingly, targeting RIPK1 for elimination has emerged as a promising anti-cancer strategy. Based on the RIPK1 inhibitor 4 previously reported by our group, we employed proteolysis targeting chimera (PROTAC) technology

Acetylcholinesterase inhibitors (AChEIs) are essential in the treatment of neurodegenerative disorders like Alzheimer’s disease, as they prevent the breakdown of acetylcholine, thereby enhancing cognitive function. This review provides a comprehensive analysis of the structural motifs and mechanisms governing AChEI pharmacological activity, with a focus on medicinal chemistry strategies to enhance

HER2-positive breast cancer remains a significant clinical challenge, often exhibiting resistance to standard therapies. This study applies a comprehensive in silico approach to identify the natural compounds with potential inhibitory effects on HER2, focusing on pharmacophore modeling, virtual screening, molecular dynamics (MD) simulations, and binding affinity estimation. Initially, 24 known HER2

Vitamin D receptor (VDR) agonists play a pivotal role in modulating immune responses and promoting melanocyte survival, making them potential candidates for vitiligo treatment. The VDR gene is integral to mediating the effects of vitamin D in the immune system, and disruptions in its structure due to missense mutations may significantly contribute to the pathogenesis of vitiligo. Missense single-nucleotide

Xanthenone fused spiro-pyrrolidine oxindoles were conveniently synthesized in good yields with high regio- and diastereoselectivity from a multicomponent synthesis involving tetrahydroxanthenones, α-amino acids, and isatins via an azomethine ylide based [3 + 2] cycloaddition process. We utilized tetrahydroxanthenone as a dipolarophile for the first time in the [3 + 2] cycloaddition of decarboxylated

AbstractThe dysregulation of the cell cycle in cancer underscores the therapeutic potential of targeting WEE1 kinase, a key regulator of the G2/M checkpoint. This study harnessed artificial intelligence (AI)-driven methodologies, particularly the MORLD platform, to identify novel WEE1 inhibitors. Starting with clinically validated WEE1 inhibitors as references, we generated 20,000 structurally diverse

Multidrug resistance (MDR) presents a major challenge for effectiveness of chemotherapy. This study investigates the effectiveness of spiroindoline quinazolinediones in reversing MDR mediated by P-glycoprotein (P-gp) overexpression in cancer cells. A series of synthesized hybrid spiro[indoline-3,2′-quinazoline]-2,4′(3′H)-dione derivatives (compounds 5a-5l) were analyzed for their ability to enhance

The global impact of emerging and re-emerging viral agents during epidemics and pandemics leads to serious health and economic burdens. Among the major emerging or re-emerging viruses include SARS-CoV-2, Ebola virus (EBOV), Monkeypox virus (Mpox), Hepatitis viruses, Zika virus, Avian flu, Influenza virus, Chikungunya virus (CHIKV), Dengue fever virus (DENV), West Nile virus, Rhabdovirus, Sandfly fever

Hsp90, or heat shock protein 90, a well-preserved molecular chaperone that is essential for the coordination of numerous biological pathways and cellular processes. Hsp90 is a molecular chaperone, which promises a target for cancer treatment. Hsp90 inhibitors are a class of drugs that have been extensively studied in preclinical models and demonstrated promise in treating a variety of illnesses, particularly

The potential downsides for the present treatment for psoriasis are drug resistance, reduced efficacy, risk of mental episodes, and drug interactions. Hence, this study aims to discover a new drug for psoriasis by considering global research efforts and exploring underrepresented chemical space regions. The objective was to identify novel PDE4D inhibitors from the dark chemical matter (DCM) database

In previous studies, we discovered YZD-7082B, a selective estrogen receptor degrader (SERD) with excellent comprehensive properties. Here, we reported the development of an efficient multigram-scale synthetic process for YZD-7082 in 13 steps. The route featured a chiral resolution of a thiochroman intermediate with a unique cis-1,2-diaryl motif using a chiral amine and a mild reduction of amide using

Telomerase, a reverse transcriptase implicated in replicative immortality of cancers, remains a challenging target for therapeutic intervention due to its structural complexity and the absence of clinically approved small-molecule inhibitors. In this study, we explored drug repurposing as a pragmatic approach to address this gap, leveraging FDA-approved drugs to accelerate the identification of potential

Biomedical knowledge graphs have emerged as powerful tools for drug discovery, but existing platforms often suffer from outdated information, limited accessibility, and insufficient integration of complex data. This study presents MedKG, a comprehensive and continuously updated knowledge graph designed to address these challenges in precision medicine and drug discovery. MedKG integrates data from

This study addresses the urgent need for new drugs to combat multi-drug-resistant tuberculosis (MDR-TB). Focusing on MmpL3, a protein essential for mycobacterial cell wall synthesis, we designed and synthesised 50 new pyrazole-based amide derivatives. These compounds were then tested for their ability to inhibit the growth of various Mycobacterium tuberculosis (Mtb) strains, including both drug-susceptible

Neuraminidase (NA) is an essential enzyme located at the outer layer of the influenza virus and plays a key role in the release of virions from infected cells. The rising incidence of global epidemics has made the urgent need for effective antiviral medications an urgent public health priority. Furthermore, the emergence of resistance caused by specific mutations in the influenza viral genome exacerbates

Azoheteroarenes-based photoswitches with high bidirectional isomerization and long thermal half-life (t1/2) have attracted widespread attention from researchers. The diversity of molecular scaffolds has a profound impact on photoswitching performance, herein, we incorporated dynamic connection sites and scaffold optimization to construct a series of pyrazolyazoindole/indazoles (PAIs)-based photoswitches

Type 2 diabetes mellitus (T2DM) is characterized by hyperglycemia and affects millions of people globally. Even after advancement and development in medical science, it is a big task to achieve victory over type 2 diabetes mellitus (T2DM). T2DM can be a reason for fatal events like stroke, cardiac failure, nephropathy, and retinopathy. Many advanced antidiabetic drugs have been introduced in the market

Herpes Simplex Virus 2 (HSV-2) infection is a global concern, affecting around 500 million individuals worldwide and being the leading cause of genital ulcers. Although several HSV vaccine candidates have been tested in humans, as of right now, neither HSV type has a licenced vaccination available. This study utilized reverse vaccinology to conduct an extensive analysis of the entire genome of HSV-2

This study systematically investigates the structure–activity relationships of 30 Ti-phenoxy-imine (FI-Ti) catalysts using machine learning (ML) approaches. Among the tested algorithms, XGBoost demonstrated superior predictive performance, achieving R2 values of 0.998 (training set) and 0.859 (test set), with a cross-validated Q2 of 0.617. Feature importance analysis identified three composite des

Novel quinoline-based derivatives 2a–e and 4a–j have been designed and synthesized as potential antiproliferative agents. The designed compounds were screened for their antiproliferative activity against sixty cell lines according to NCI protocol. The promising hybrids 4d–g are screened by MTT assays on three cancer cell lines: leukemia (MOLT-4), lung cancer (HOP-92), and breast cancer (T47D), with

The development of multifunctional agents has been a heated area of research for AD treatment in recent years. In this work, a series of melatonin-isatin hybrids were designed, synthesized, and evaluated as multifunctional agents for treating AD. In vitro studies indicated that most of the synthesized compounds displayed moderate to good MAO-B inhibition activities and good antioxidant activities.

This study investigates the potential of novel thiazole and hydroxybenzohydrazide derivatives as antitubercular agents. Using molecular docking and density functional theory (DFT) calculations, the binding affinities of these derivatives to the enoyl-acyl carrier protein reductase (InhA) enzyme of M. tb were assessed. InhA is crucial for the mycobacterial fatty acid synthase II (FAS-II) pathway, making

AKT1, a serine/threonine kinase, is pivotal in signaling and regulating cell survival, proliferation, and metabolism. This review focuses on the structural insights and the essential features required for its active conformation. AKT belongs to the AGC kinase group and has three isoforms: AKT1, AKT2, and AKT3. AKT has three functional regions: PH domain, kinase domain, and hydrophobic motif. AKT1 activation

Antineoplastic drugs are becoming prevalent due to increasing cancer casualties around the globe. However, the adverse effects of these drugs are evident due to limited insight into the underlying mechanisms that result in non-specific binding and consequent off-target toxicity. The study investigates the side effects of an antineoplastic drug, Capecitabine, a prodrug converted into fluorouracil by

Sparganii Rhizoma (SR) has demonstrated promising anticancer effects across various malignancies; however, its mechanisms in laryngeal cancer (LC) remain poorly understood. This study employs network pharmacology and molecular docking to investigate the molecular mechanisms underlying SR’s therapeutic effects on LC, providing novel insights for its potential use in treatment. Active compounds and targets

Acute respiratory distress syndrome (ARDS) is the leading cause of mortality in pathogen-mediated lung inflammation. Viral-induced cytokine release syndrome (CRS) has emerged as a global pandemic, characterized by a hyperactive immune response and excessive cytokine production causing irreversible lung injury. This study aimed to evaluate FDA-approved drugs for their potential to target hyperactive

α-Glucosidase inhibitors (AGIs) are pharmacological agents commonly used to manage postprandial hyperglycemia associated with type 2 diabetes mellitus (T2DM). Developing novel, potent AGIs remains a significant area of research. In this study, we investigated a series of derivatives of the natural product from α-mangostin as potential AGIs. A combined experimental and computational approach was employed

Helicobacter pylori (H. pylori, Hp) is a primary contributor to various stomach diseases, including gastritis and gastric cancer. This bacterium can colonize gastric epithelial cells, compromising their integrity and leading to the development of these conditions. While antibiotics are the mainstay of treatment for H. pylori infections, their widespread use has led to serious issues with drug resistance

A series of novel dual-action statin conjugates, which exhibit both triglyceride and cholesterol lowering activities, have been systematically designed, synthesized, and subjected to comprehensive pharmacological evaluation. All the target compounds were characterized by 1HNMR, 13CNMR, and HRMS. Biological evaluation demonstrated that the majority of the synthesized compounds exhibited significant

This study investigated the molecular targets and pathways modulated by pterostilbene in breast cancer using network pharmacology and in vitro analysis. The structure of chemicals of pterostilbene was retrieved from PubChem, and gene targets were predicted through Swiss Target Prediction. Human-specific targets were validated using UniProtKB and breast cancer-related targets were identified using GeneCards

Two new series of pyrimidinyl ethyl pyrazoles derivatives 13a–f and 14a–f were designed and synthesized to possess both anticancer effect by inhibiting BRAFV600E and anti-inflammatory effect by inhibiting JNK isoforms. The structure of the new compounds was generated from hybridization of two main moieties. The pyrimidinyl moiety from reported BRAFV600E inhibitors, and the pyrazole moiety from JNK

The viability of cells and the integrity of the genome depend on the detection and repair of damaged DNA through intricate mechanisms. Cancer treatment employs chemotherapy or radiation therapy to eliminate neoplastic cells by causing substantial damage to their DNA. In many cases, improved DNA repair mechanisms lead to resistance to these medicines; therefore, it is essential to expand efforts to

Phosphoinositide 3-kinases (PI3Ks) phosphorylate phosphoinositides on the membrane, which act as secondary signals for various cellular processes. PI3Kα, a heterodimer of the p110α catalytic subunit and the p85α regulatory subunit, is activated by growth factor receptors or mutations. Among these mutations, E545K present in the helical domain is strongly associated with cancer, and is known to disrupt

A series of flavonol derivatives containing benzothiazole were designed and synthesized. The structures of all the compounds were characterized by NMR and HRMS. The results of the activity assay showed that some of the target compounds possessed outstanding in vivo antiviral activity against the tobacco mosaic virus (TMV). Among them, the median effective concentration (EC50) of L20 was 90.5 and 202

Epigenetic regulation intricately governs cellular mechanisms, including proliferation, death, differentiation, and cell cycle orchestration. One such target, Enhancer of zeste homolog 2 (EZH2), is essential for epigenetic regulation. EZH2 trimethylates histone H3 lys27 (H3K27me3), inhibiting target gene transcription and promoting chromatin condensation, thereby initiating tumorigenesis, thus a potentially