Phytochemicals from Daucus carota have therapeutic potential against Triple-Negative Breast Cancer PDK1 and PLK1. DOI Creative Commons
Kayode Yomi Raheem, Modinat Aina Abayomi, Oluwatosin Maryam Adeyemo

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Ноя. 6, 2024

Abstract Triple-negative breast cancer (TNBC) is a deadly form of that lacks estrogen, progesterone, and HER2 receptors. The development drugs for TNBC has been challenging due to the lack specific therapeutic targets. However, recent studies have shown targeting ATP active PDK-1 PLK-1 proteins could be potential drug targets treatment. New medications considerable adverse effects, highlighting need more targeted effective therapies. In this study, we employed various computational approaches, including molecular docking, dynamics (MD) simulations, pharmacokinetic studies, binding free energy calculations, principal component analysis (PCA), alanine scanning analysis, identify bioactive compounds from Daucus carota- extracted natural can bind these ATP-binding sites inhibit activity PDK1 PLK1. Our study revealed eight showed reasonably good docking scores, energies, ADMET properties against PLK1 enzymes. Astragalin scolimoside substantial affinity persistent interactions in pocket region two proteins. Further MD simulation 150 ns also suggested were stably bound site with very minor fluctuations. We believe identified hits carota will performing biological assays.

Язык: Английский

System biology-based assessment of the molecular mechanism of IMPHY000797 in Parkinson’s disease: a network pharmacology and in-silico evaluation DOI Creative Commons
Gomathy Subramanian,

Hannah Lalengzuali Fanai,

Jagdish Chand

и другие.

Scientific Reports, Год журнала: 2024, Номер 14(1)

Опубликована: Окт. 8, 2024

IMPHY000797 derivatives have been well known for their efficacy in various diseases. Moreover, found to modulate such genes involved multiple neurological disorders. Hence, this study seeks identify and the probable molecular mechanism that could be pathogenesis of Parkinson's disease. The utilized biological tools as DisGeNET, STRING, Swiss target predictor, Cytoscape, AutoDock 4.2, Schrodinger suite, ClueGo, GUSAR. All reported were obtained using further, common incorporated into STRING get KEGG pathway, all data was converted a protein/pathway network via Cytoscape. clustering performed gene-enriched two-sided hypergeometrics (p-value). binding affinity verified with highest regulated 25 proteins utilizing "Monte Carlo iterated search technique" "Emodel Glide score" function. Three thousand five hundred eighty-three identified disease 31 compound, among which identified. Further, "FOXO-signaling pathway" modulated pathway. Among proteins, exhibited by SIRT3, FOXO1, PPARGC1A compound IMPHY000797. rat toxicity analysis provided safety compound. required mechanism, needs more confirmation from other studies, is still significant hit-back.

Язык: Английский

Процитировано

2
Inhibitory effect of Sinapic acid derivatives targeting structural and non-structural proteins of dengue virus serotype 2: An in-silico assessment DOI Creative Commons
Miah Roney, Amit Dubey,

Normaiza Zamri

и другие.

Aspects of Molecular Medicine, Год журнала: 2023, Номер 2, С. 100028 - 100028

Опубликована: Ноя. 10, 2023

DENV infects 50–100 million individuals, and 500,000 of them go on to acquire the more serious dengue hemorrhagic fever, which causes around 20,000 fatalities every year. Despite its widespread nature, there is no medication licenced treat this condition. The purpose work identify anti-DENV medicines from sinapic acid (SA) derivatives utilising in-silico evaluation through docking pharmacokinetics investigations. For DENV-2 envelop protein, 1-O-β-d-glucopyranosyl sinapate had a significant score −7.7 kcal/mol, while sinapoyl malate −6.7 kcal/mol for NS2B/NS3 protein. Additionally, according PASS server, have wide range enzymatic activities since their probability active (Pa) values > 0.700. These compounds exhibit numerous pharmacological effect activating body's enzymes, analyses pharmacokinetic qualities. Accordingly, these substances showed acute toxicity rates at LD50 log10 (mmol/g) (mg/g) concentrations when administered via various routes, including intraperitoneal, intravenous, oral, subcutaneous. result research suggests, may function as possible inhibitors halt DENV, in-vitro in-vivo required validate activity other features.

Язык: Английский

Процитировано

4
Phytochemicals from Daucus carota have therapeutic potential against Triple-Negative Breast Cancer PDK1 and PLK1. DOI Creative Commons
Kayode Yomi Raheem, Modinat Aina Abayomi, Oluwatosin Maryam Adeyemo

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Ноя. 6, 2024

Abstract Triple-negative breast cancer (TNBC) is a deadly form of that lacks estrogen, progesterone, and HER2 receptors. The development drugs for TNBC has been challenging due to the lack specific therapeutic targets. However, recent studies have shown targeting ATP active PDK-1 PLK-1 proteins could be potential drug targets treatment. New medications considerable adverse effects, highlighting need more targeted effective therapies. In this study, we employed various computational approaches, including molecular docking, dynamics (MD) simulations, pharmacokinetic studies, binding free energy calculations, principal component analysis (PCA), alanine scanning analysis, identify bioactive compounds from Daucus carota- extracted natural can bind these ATP-binding sites inhibit activity PDK1 PLK1. Our study revealed eight showed reasonably good docking scores, energies, ADMET properties against PLK1 enzymes. Astragalin scolimoside substantial affinity persistent interactions in pocket region two proteins. Further MD simulation 150 ns also suggested were stably bound site with very minor fluctuations. We believe identified hits carota will performing biological assays.

Язык: Английский

Процитировано

0