Recently, the world has been witnessing a global pandemic with no effective therapeutics yet, while cancer continues to be major disease claiming many lives. The natural compound curcumin is bestowed multiple medicinal applications in addition demonstrating antiviral and anticancer activities. In order elucidate impact of on COVID-19 cancer, current investigation adapted several computational techniques unfold its possible inhibitory activity. Accordingly, similar compounds analogues were...

Protein tyrosine phosphatase 1B (PTP1B) is one of the target enzymes whose disruption leads to obesity and diabetes. A series PTP1B inhibitors were isolated from leaves Artocarpus elasticus, used in traditional medicines for The (1–13), including two new compounds (1 2), consisted dihydroflavonols flavones. structural requirements inhibitory mode potency revealed both skeletons. highest properties dihydroflavonol 1 flavone 6 analogs with IC50 values 0.17 0.79 μM, respectively....

The rapid spread of COVID-19, caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a worldwide health emergency. Unfortunately, to date, very small number remedies have been be found effective against SARS-CoV-2 infection. Therefore, further research required achieve lasting solution this deadly disease. Repurposing available drugs and evaluating natural product inhibitors target proteins could an approach accelerate drug discovery development. With strategy...

Owing to several mutations, the oncogene Kirsten rat sarcoma 2 viral homolog (KRAS) is activated in majority of cancers, and targeting it has been pharmacologically challenging. In this study, using an silico approach comprised pharmacophore modeling, molecular docking, dynamics simulations, potential KRAS G12D inhibitors were investigated. A ligand-based common feature model was generated identify framework necessary for effective inhibition. The chemical features selected two hydrogen bond...

Abstract Regulated in development and DNA damage response 1 (REDD1) expression is upregulated to metabolic imbalance obesity. However, its role obesity-associated complications unclear. Here, we demonstrate that the REDD1–NF-κB axis crucial for inflammation dysregulation. Mice lacking Redd1 whole body or adipocytes exhibited restrained diet-induced obesity, inflammation, insulin resistance, hepatic steatosis. Myeloid Redd1- deficient mice showed similar results, without obesity -deficient...

The mammalian target of rapamycin (mTOR) is a serine/threonine kinase portraying quintessential role in cellular proliferation and survival. Aberrations the mTOR signaling pathway have been reported numerous cancers including thyroid, lung, gastric ovarian cancer, thus making it therapeutic target. To attain this objective, an silico investigation was designed, employing pharmacophore modeling approach. A structure-based (SBP) model exploiting key features selective inhibitor, Torkinib...

The transgenic rice cultivar of Oryza sativa spp. japonica cv. Hwa-Young, C1/R-S (C1/R-S rice), is a flavonoid-rich rice. grains were extracted with aqueous MeOH, and the concentrated extract was partitioned EtOAc, n-BuOH, H2O, successively. Repeated silica gel, octadecyl gel (ODS), Sephadex LH-20 column chromatographies for EtOAc n-BuOH fractions afforded four new flavonoids (compounds 2, 3, 7, 8) along known flavonoids: (+)-3′-O-methyltaxifolin (1), brassicin (4),...

The cyclin-dependent kinase 7 (CDK7) plays a crucial role in regulating the cell cycle and RNA polymerase-based transcription. Overexpression of this is linked with various cancers humans due to its dual involvement development. Furthermore, emerging evidence has revealed that inhibiting CDK7 anti-cancer effects, driving development novel more cost-effective inhibitors enhanced selectivity for over other CDKs. In present investigation, pharmacophore-based approach was utilized identify...

Spleen tyrosine kinase (SYK) is an essential mediator of immune cell signaling and has been anticipated as a therapeutic target for autoimmune diseases, notably rheumatoid arthritis, allergic rhinitis, asthma, cancers. Significant attempts have undertaken in recent years to develop SYK inhibitors; however, limited success achieved due poor pharmacokinetics adverse effects inhibitors. The primary goal this research was identify potential inhibitors having high affinity, selectivity based on...

Protein acetylation and deacetylation play vital roles in the structural physiological behavior of target proteins. Histone deacetylase 6 (HDAC6) remains a key therapeutic several chronic diseases such as cancer, neurodegenerative, hematological diseases. In tau-pathogenesis, HDAC6 tightly regulates microtubule-associated tau physiology, its inhibition suppresses Alzheimer's phenotype. To this end, current study has identified novel inhibitors by structure-based drug designing method. A...

Drug resistance is a core issue in cancer chemotherapy. A known folate antagonist, methotrexate (MTX) inhibits human dihydrofolate reductase (hDHFR), the enzyme responsible for catalysis of 7,8-dihydrofolate reduction to 5,6,7,8-tetrahydrofolate, biosynthesis and cell proliferation. Structural change DHFR significant cause subsequent loss MTX. In current study, wild type hDHFR double mutant (engineered variant) F31R/Q35E (PDB ID: 3EIG) were subject computational study. Structure-based...

Breast cancer (BC) is the leading cause of death among women worldwide devoid effective treatment. It therefore important to develop agents that can reverse, reduce, or slow growth BC. The use natural products as chemopreventive provides enormous advantages. aim current investigation determine efficacy phytochemicals against BC along with approved drugs screen most desirable and phytocompound. In study, 36 have been evaluated aromatase identify potential candidate drug employing Cdocker...

Background: Activated Cdc42-associated kinase (ACK1) is essential for numerous cellular functions, such as growth, proliferation, and migration. ACK1 signaling occurs through multiple receptor tyrosine kinases; therefore, its inhibition can provide effective antiproliferative effects against human cancers. A number of ACK1-specific inhibitors were designed discovered in the previous decade, but none have reached clinic. Potent selective are urgently needed. Methods: In present investigation,...

Dihydrofolate reductase (DHFR) is an essential cellular enzyme and thereby catalyzes thereduction of dihydrofolate to tetrahydrofolate (THF). In cancer medication, inhibition humanDHFR (hDHFR) remains a promising strategy, as it depletes THF slows DNA synthesis cellproliferation. the current study, ligand-based pharmacophore modeling identified evaluatedthe critical chemical features hDHFR inhibitors. A model (Hypo1) was generatedfrom known inhibitors DHFR with correlation coefficient...

Abstract The mitochondrial calcium uniporter (MCU) plays essential roles in homeostasis and regulates cellular functions, such as energy synthesis, cell growth, development. Thus, MCU activity is tightly controlled by its regulators well post-translational modification, including phosphorylation protein kinases proline-rich tyrosine kinase 2 (Pyk2) AMP-activated (AMPK). In our vitro assay, the N-terminal domain (NTD) was phosphorylated C isoforms (PKC βII , PKC δ ε ) localized matrix....

DDX3 belongs to RNA helicase family that demonstrates oncogenic properties and has gained wider attention due its role in cancer progression, proliferation transformation. Mounting reports have evidenced the of cancers making it a promising target abrogate triggered cancers. Dual pharmacophore models were generated subsequently validated. They used as 3D queries screen InterBioScreen database, resulting selection curcumin was escalated molecular dynamics simulation studies. In vitro...

Protein-protein interactions are indispensable physiological processes regulating several biological functions. Despite the availability of structural information on protein-protein complexes, deciphering their complex topology remains an outstanding challenge. Raf kinase inhibitory protein (RKIP) has gained substantial attention as a favorable molecular target for numerous pathologies including cancer and Alzheimer’s disease. RKIP interferes with RAF/MEK/ERK signaling cascade by...

Progeria is a rare genetic disorder characterized by premature aging that eventually leads to death and noticed globally. Despite alarming conditions, this disease lacks effective medications; however, the farnesyltransferase inhibitors (FTIs) are hope in dark. Therefore, objective of present article identify new compounds from databases employing pharmacophore based virtual screening. Utilizing nine training set along with lonafarnib, common feature was constructed consisting four features....

Breast cancer is one of the major causes mortalities noticed in women globally. DDX3 has emerged as a potent target for several cancers, including breast to which currently there are no reported or approved drugs.To find effective therapeutics, three compounds were computationally designed tweaking structure natural compound butein. These synthesized and evaluated their anticancer property MCF-7 MDA-MB-231 cell lines targeting DDX3. The silico molecular docking studies have shown that...

Cysteine-cysteine chemokine receptor 5 (CCR5) has been discovered as a co-receptor for cellular entry of human immunodeficiency virus (HIV). Moreover, the role CCR5 in variety cancers and various inflammatory responses was also discovered. Despite fact that several antagonists have investigated clinical trials, only Maraviroc licensed use treatment HIV patients. This indicates there is need novel antagonists. Keeping this mind, present study designed. The active inhibitors with known IC50...