This site uses cookies to improve your experience. To help us insure we adhere to various privacy regulations, please select your country/region of residence. If you do not select a country, we will assume you are from the United States. Select your Cookie Settings or view our Privacy Policy and Terms of Use.
Cookie Settings
Cookies and similar technologies are used on this website for proper function of the website, for tracking performance analytics and for marketing purposes. We and some of our third-party providers may use cookie data for various purposes. Please review the cookie settings below and choose your preference.
Used for the proper function of the website
Used for monitoring website traffic and interactions
Cookie Settings
Cookies and similar technologies are used on this website for proper function of the website, for tracking performance analytics and for marketing purposes. We and some of our third-party providers may use cookie data for various purposes. Please review the cookie settings below and choose your preference.
Strictly Necessary: Used for the proper function of the website
Performance/Analytics: Used for monitoring website traffic and interactions
This study investigates the neuroprotective effects of Kisspeptin-54 in ischemic stroke. In mice with induced stroke, Kisspeptin-54 reduced brain damage, improved neurological function, and restored occludin levels, strengthening the bloodbrain barrier. The findings reveal that Kisspeptin-54 enhances endothelial resilience through GATA-4-driven occludin expression, suggesting a promising therapeutic approach for stroke treatment.
Synthesis of benzoheteraryl thioacetamide derivatives 4-6 and thiazolyl aminopyrazole derivative 9. Synthesis of thiazolyl pyrazolo[1,5- a ]pyrimidine derivatives 10-13 and 17. Synthesis of thiazolyl pyrazolo[1,5- a ]pyrimidine derivatives 18-22. The antimicrobial efficacy of the newly synthesized compounds was studied extensively. The molecular docking investigation revealed the presence of many derivatives with high binding affinities and distinct interaction.
CRISPR-CAS9 is an innovative gene editing technology to precisely remove or incorporate into the gene of interest; CRISPR-CAS9 shows promising results in HIV treatment. ABSTRACT Clustered regularly interspaced short palindromic repeats (CRISPR/Cas system) is now the predominant approach for genome editing. Compared to conventional genetic editing methods, CRISPR/Cas technology offers several advantages that were previously unavailable.
Although it is currently only used in veterinary therapy, carprofen proves to be a molecule with a versatile therapeutic potential for human pharmacotherapy. Moreover, the molecule is a target in the drug discovery process for the development of new bioactive compounds. ABSTRACT Carprofen, a nonsteroidal anti-inflammatory drug (NSAID) derived from propanoic acid, is known for its analgesic and antipyretic properties.
Quercetin is the core component of Hedyotis diffusa against breast cancer (BRCA). CDK1, BIRC5, and HSP90AA1 play key roles in the anti-BRCA effect of Hedyotis diffusa. ABSTRACT Hedyotis diffusa , a famous Traditional Chinese Medicine (TCM), has been extensively used clinically for thousands of years. Although the therapeutic effect of Hedyotis diffusa on tumors has attracted wide attention, components, and mechanisms against breast cancer (BRCA) have not been fully understood.
The [2,3]-isoxazole 4 and [2,3]-pyrazole 5 of 28-oxo-allobetulone exhibited high inhibitory activity against the Flu A/Puerto Rico/8/34 (H1N1) virus, with hemagglutinin HA IC 50 values of 7.3M (SI 86) and 62.1M (SI 10), respectively, acting primarily at the early stages of the viral cycle. Molecular docking revealed their binding near the HA1-HA2 interface of hemagglutinin, preventing virion binding to cell receptors.
Isocitrate dehydrogenase (IDH) is a key metabolic enzyme that catalyzes the conversion of isocitrate to -ketoglutaric acid (-KG). At present, there are few studies on the drug resistance of mIDH1 inhibitors. Therefore, this article first summarizes terms of IDH1 function from the molecular mechanism of IDH1, the mechanism of mutation, and the metabolism of substances due to mutations.
A multi-objective optimization algorithm incorporating the strategies of dynamic semi-parameter adaptation updating, gradient enhancement, and population size reduction is adopted to solve the problem of protein-ligand docking. ABSTRACT Molecular docking, which simulates the binding pose of a drug molecule to target proteins and predicts the binding affinity, is an important computational tool in structure-based drug discovery.
ABSTRACT Diketopiperazines (DKPs) have emerged as promising candidates for treating diverse diseases, particularly cancer. In this context, 2,5-diketopiperazines have been extensively investigated in comparison with 2,6-diketopiperazines. This work explores the selectivity and impact of 2,6-diketopiperazine enantiomers derived from -amino acids on MDA-MB-231 triple-negative breast cancer cells (TNBC).
Synthesis and anticancer studies of spiro[indoline-oxirane] derivatives. ABSTRACT Epoxides are well-known compounds as anticancer agents. In this article, we present the synthesis of novel 3-phenyl-1-((1-aryl-1 H -1,2,3-triazol-5-yl)methyl)spiro[indoline-3,2-oxiran]-2-one derivatives by the regioselective reaction of sulfur ylides with 1,2,3-triazole-tethered isatins and their anticancer effects on hepatocellular carcinoma (HCC) cells HepG2 and HCCLM3.
The review provides a comprehensive analysis of non-hydroxamate inhibitors for IspC, an enzyme crucial in the MEP pathway, highlighting its structural diversity and improved drug development potential. It details the design strategies for lipophilic and bisubstrate non-hydroxamate inhibitors, emphasizing their enhanced metal-ion coordination and increased inhibitory potency against IspC.
Artesunate suppressed the migration and invasion of thyroid cancer cells via inhibiting the PI3K/Akt pathway by PTEN upregulation-blocked M2 polarization of tumor-associated macrophages. ABSTRACT Immunotherapy holds promise for thyroid cancer (TC) treatment. In the context of our previous findings that artesunate (ART) could inhibit the migration and invasion of TC cells through phosphoinositide 3-kinase/protein kinase B (PI3K/Akt), this study was engineered to investigate whether ART regulates
This review highlights recent advancements in small molecule inhibitors targeting Cdc2-like kinase 4 (Clk4), emphasizing their potential in treating cancers and neurodegenerative diseases. It explores structure-activity relationships, binding modes, and challenges in developing selective Clk4 inhibitors, offering insights for future therapeutic strategies.
Fragment-based drug discovery (FBDD) was applied to cytochrome P450 3A4 reconstituted in Nanodiscs (NDs) with various lipid compositions. The choice of ND lipid influenced drug membrane interactions and fragment hit rates, demonstrating the critical role of the membrane environment in fragment screening for membrane proteins. ABSTRACT Membrane proteins (MPs) are important yet challenging targets for drug discovery.
Design and synthesis of pyrrole-tethered bisbenzoxazole (PTB) derivatives reveal potent anticancer activity against MCF-7 breast cancer cells. Compounds B8 , B14 , and B18 exhibit ~20-fold lower IC 50 values than tamoxifen, induce early-stage apoptosis, and arrest the cell cycle at the G1 phase via caspase-9 activation. These findings position PTB derivatives as promising candidates for targeted breast cancer therapy.
We have discovered a novel non-covalent MurA inhibitor as an antibacterial agent through machine learning and bioactivity testing. This is the first to use machine learning for virtual screening of non-covalent inhibitors of MurA. ABSTRACT The bacterial cell wall is crucial for maintaining the integrity of bacterial cells. UDP-N-acetylglucosamine 1-carboxyethylene transferase (MurA) is an important enzyme involved in bacterial cell wall synthesis.
Synthesis, structureactivity relationship, targets, and anticancer activity of fused and substituted piperazines. ABSTRACT Cancer is an abnormal and uncontrolled proliferation of normal cells. The availability of safer anticancer drugs with exceptional selectivity for healthy cells and great efficacy against various cancer forms continues to be a significant obstacle.
We reported a virtual screening workflow combining docking and MD simulations to achieve eight compounds for further enzymatic assay and ADMET profile prediction. The results indicated a candidate 2 with IC 50 values of 2.396 and 5.996M against LRRK2 and LRRK2 G2019S, respectively, implying the reliability of this approach. ABSTRACT Parkinson's disease (PD) is the second most common neurodegenerative disease but has limited medications.
A series of novel chalcone Mannich base derivatives were successfully synthesized. Among them, most of the target compounds exhibited strong activities against five different tumor cells. Furthermore, compound I 4 , which has the most potential activity, could induce apoptosis in A549 and A549/DDP cells. ABSTRACT A novel class of chalcone Mannich base derivatives I 1-9 and II 1-11 was synthesized, which exhibited significant antiproliferation activities in five different cancer cells.
A combination of network pharmacology and invitro validation was used to reveal the potential targets and molecular mechanisms of resveratrol for CRS treatment. ABSTRACT Resveratrol (RES) is a polyphenolic antioxidant derived from different plant products, which has anti-inflammatory and antioxidative stress effect. However, the effect of resveratrol on chronic rhinosinusitis (CRS) still lacks systematic research.
Analysis of prevalence of ring, nonring, sp 3 -, and sp 2 -hybridized oxygen in approved drugs. For the first time, analysis of distribution of different types of oxygen from center of mass of a molecule. ABSTRACT Despite advancements in molecular design rules and understanding biochemical processes, the field of drug design and discovery seeks to minimize the number and duration of synthesis-testing cycles to convert lead compounds into drug candidates.
An in-house molecule library was screened using in silico molecular docking, and a myo-inositol derivative was identified as a potent hit molecule. The invitro biochemical assays validated that J1-65 inhibits PTP-PEST activity competitively and the inhibitor binding stabilizes the protein-ligand complex. ABSTRACT PTP-PEST (also known as PTPN12) regulates cellular signaling and transduction pathways by dephosphorylating its substrate.
The remarkable therapeutic potential of luteolin against cervical cancer can be ascribed to its profound influence on amino acid and nucleotide metabolism, substantiated by the seamless integration of metabolomics, bioinformatics, and molecular docking techniques in this comprehensive investigation. ABSTRACT The incidence of cervical cancer is high among women globally.
This study investigates the effects and mechanisms of combining Polyphyllin VII (PPVII) with Docetaxel (DTX) in the treatment of prostate cancer (Pca). Experiments were conducted using DTX-sensitive DU-145 cells and DTX-resistant DU145/DTX cells. The results indicate that PPVII significantly enhanced the inhibitory effect of DTX, reduced cell viability, and promoted apoptosis and cell cycle arrest.
The future of treating challenging fungal infections lies in novel therapies targeting new antifungal targets, overcoming resistance mechanisms, and exploring innovative dual inhibitors. ABSTRACT Invasive fungal infections (IFIs) pose significant challenges in clinical settings, particularly due to their high morbidity and mortality rates. The rising incidence of these infections, coupled with increasing antifungal resistance, underscores the urgent need for novel therapeutic strategies.
Among prepared 2-phenyl- N -(pyridin-2-yl)acetamides, we identified compounds with promising invitro antimycobacterial activity (notably compound 12 ). In comparison with the previous series, the methylene-extended linker improved antimycobacterial activity. Compound 26 was identified as a promising antiproliferative hit. ABSTRACT Infectious diseases, including bacterial, fungal, and viral, have once again gained urgency in the drug development pipeline after the recent COVID-19 pandemic.
A depression database was first constructed, and simvastatin was used as an input to predict potential targets using machine/deep learning methods. Interestingly, the P2X7/NLRP3 pathway was predicted as a potential target for simvastatin. Subsequent Animal experiment's results confirmed this predict. ABSTRACT Depression is a mental health disorder and is the fourth most prevalent disease.
Peptidedrug conjugates (PDCs) were produced by combining a cancer selective cell-penetrating peptide (PDIP) with camptothecin (CPT). The PDCs crossed membranes and cleavable PDCs killed melanoma cells with nanomolar potency. ABSTRACT Drug targeting strategies, such as peptidedrug conjugates (PDCs), have arisen to combat the issue of off-target toxicity that is commonly associated with chemotherapeutic small molecule drugs.
5(4-Hydroxyphenyl)-2-(N-Phenyl amino)-1,3,4-Oxadiazole (Hppo) can considered as a versatile agent in designing novel pharmaceuticals. ABSTRACT Oxadiazole compounds are of great interest because they have a range of biological activities ranging from antioxidants to anticancer agents. Against this background, we wanted to demonstrate the antioxidant, enzyme inhibitory, and anticancer effects of 5(4-hydroxyphenyl)-2-(N-phenylamino)-1,3,4-oxadiazole (Hppo).
Seventeen new benzimidazole-hydrazone derivatives ( 4a-4r ) were designed and synthesized. Compounds 4a-4r were searched for their invitro inhibitory effects against hCA I and hCA II isozymes and IC 50 values were determined. Compound 4k , a 4-methoxyphenyl derivative, showed the most potent inhibitory activity against hCA isoenzymes. The in silico molecular docking analysis and the ability of the synthesized analogs to inhibit hCA I were also examined.
Compounds 7h and 7 in HTB-9 and compounds 7a and 7 in HT-29 cell line demonstrated most cytotoxic activity among all compounds. These compounds expectedly increased apoptosis, activated caspase 3/7, and inhibited migration in both cell lines compared to controls. As a remarkable result, a greater apoptotic index was observed in HT-29 cells treated with compound 7 than those of cisplatin-treated cells.
This diagram illustrates the proposed mechanism by which Schisandrin A (SchA) affects hepatocellular carcinoma (HCC) cells. SchA induces reactive oxygen species (ROS) generation in mitochondria, leading to oxidative stress and mitochondrial dysfunction. This cascade activates AMP-activated protein kinase (AMPK), which inhibits the mTOR pathway, resulting in decreased cell proliferation and increased apoptosis.
The new palmitoylated derivatives of thioglycolic acid are designed to mimic microbial lipopeptides as a new class of small-molecule immunomodulators. The most active compound ( 10 ) induced a 1226-fold increase in the expression of TNF- and IL-1 mRNA and triggered a marked release of NO in isolated macrophages at 1.0M. ABSTRACT The immune system is essential for the defense against infections and is critically implicated in various disorders, including immunodeficiency, autoimmunity, inflammati
The results of invivo anti-inflammatory tests showed that compound 5k was the most potent of the mollugin derivatives with an inhibition rate of 81.77%, which was significantly more potent than or the positive control drugs (ibuprofen and mesalazine). ABSTRACT Nuclear factor B (NF-B) is a key inducible transcription factor that controls a large number of genes involved in inflammatory and immune processes.
We have discovered a gefitinib derivative that can inhibit IDO1 enzyme activity in Hela cells, thereby inducing apoptosis in these cells. ABSTRACT Cervical cancer is the fourth most common cancer among women globally. Its development is closely linked to accelerated cell cycle progression and the inhibition of apoptosis in cervical cancer tissues. Gefitinib has demonstrated efficacy in inhibiting cervical cancer cells, and the 1,2,3-triazole structure is widely recognized for its role in inducin
Tectorigenin could reduce the expression levels of inflammatory cytokines in both DBV-infected THP-1 cells and plasma samples of IFNAR / mice infected with DBV. ABSTRACT Severe fever with thrombocytopenia syndrome (SFTS) is a severe emerging infectious disease caused by Dabie bandavirus (DBV). Tectorigenin has been demonstrated to exert anti-inflammatory effect.
The stabilization of the G-quadruplex region in the c-Myc and Bcl-2 promoter genes by voreloxin leads to the downregulation of c-Myc and Bcl-2 expression, resulting in apoptosis of leukemia cells. ABSTRACT Overexpression of c-Myc is a key factor in the development of leukemia and other malignancies, highlighting the urgent need for novel drugs to inhibit c-Myc protein levels.
EXPRESSION OF CONCERN: Y. Liu, D. Cheng, M. Ge, and W. Lin, The Truncated Human Telomeric Sequence Forms a Hybrid-Type Intramolecular Mixed Parallel/antiparallel G-quadruplex Structure in K+ Solution, Chemical Biology & Drug Design 88, no. 1 (2016): 122-128, [link]. This Expression of Concern is for the above article, published online on 12 February 2016, in Wiley Online Library ( [link] ), and has been issued by agreement between the journal Editor-in-Chief, Roberta Melander; and John Wiley
The inhibitory profile of triaminopyrimidines was expanded and low nM IC 50 alky and aryl variants of CK-1-41 were discovered. Docking supported previous work indicating allosteric inhibition of caspase-1. Analogs with electrophilic warheads were created and inhibited caspase-1 in a partially reversible, time-dependent manner with experimental and docking results supporting allostery.
We organize all of the trending information in your field so you don't have to. Join 15,000+ users and stay up to date on the latest articles your peers are reading.
You know about us, now we want to get to know you!
Let's personalize your content
Let's get even more personalized
We recognize your account from another site in our network, please click 'Send Email' below to continue with verifying your account and setting a password.
100 
Let's personalize your content