In silico analysis of Diosmetin as an effective chemopreventive agent against prostate cancer: molecular docking, validation, dynamic simulation and pharmacokinetic prediction-based studies

Journal of Biomolecular Structure and Dynamics, Год журнала: 2023, Номер unknown, С. 1 - 13

Опубликована: Авг. 24, 2023

Prostate cancer is the second most dangerous type worldwide. While various treatment options are present i.e. agonists and antagonists, their utilization leads to adverse effects due this resistance developing, ultimately outcome remission. So, overcome issue, we have undertaken an in-silico investigation identify promising unique flavonoid candidates for combating prostate cancer. Using GOLD software, study assessed effectiveness of 560 natural secondary polyphenols against CDKN2. Protein Data Bank was used retrieve 3D crystal structure CDKN2 (PDB Id: 4EK3) retrieved selected from PubChem database. The compound Diosmetin shows highest score with which 58.72. To better understand 2-dimensional 3-dimensional interactions, interacting amino acid residues were visualised using Discovery Studio 3.5 Maestro 13.5. Schrodinger-Glide, re-docked, decoy ligands docked CDKN2, further ascertain study. Gold forecasted pharmacokinetics characteristics, results tabulated analysed. Utilising Gromacs software Desmond packages, 100 ns molecular dynamics simulations run evaluate structural persistence variations protein-ligand complexes. Additionally, our revealed that had a binding affinity measuring 58.72, it also showed remarkable stability across 100-ns simulation. Thus, following in-vitro in-vivo clinical studies, diosmetin might lead regimen.Communicated by Ramaswamy H. Sarma.

Язык: Английский

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Synthesis, biological evaluation, and computational studies of thiazolyl hydrazone derivatives as triple mutant allosteric EGFR inhibitors

Journal of the Chinese Chemical Society, Год журнала: 2024, Номер 71(7), С. 706 - 720

Опубликована: Июнь 11, 2024

Abstract Herein, new thiazole‐2‐yl‐based hydrazone derivatives were synthesized and assessed for in vitro anticancer activity against wild type A549, MCF7, DU145, mutant H1975 cancer cell lines by 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assay. Among all, 4‐(4‐Chlorophenyl)‐2‐(2‐((4‐methylthiazol‐5‐yl)methylene)hydrazineyl)thiazole ( 4b ) elicited prominent wild‐type epidermal growth factor receptor (WT‐EGFR) MCF7 line with an IC 50 value of 9.57 ± 1.80 μM, whereas 4‐Methyl‐5‐((2‐(4‐(4‐nitrophenyl)thiazol‐2‐yl)hydrazineylidene)methyl)thiazole 4c showed appreciable 11 0.7 μM the mutated EGFR lung cells. Doxorubicin Osimertinib used as standard drugs comparison activity. Compound significantly increased early apoptosis (30.2%) late (7.6%) at a 5 concentration control (early 2.5%, 1.2%). The molecular docking study was performed (T790M/C797S) PDB: 5D41 enzyme to gain information about interactions molecules binding pockets. Moreover, ADME dynamic simulation studies accomplished insight into drug‐likeness conformational stability, respectively. findings demonstrate promising alignment between observed effects computational analyses.

Язык: Английский

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COMPUTATIONAL THERAPEUTIC REPURPOSING OF TAVABOROLE TARGETING ARGINASE-1 FOR VENOUS LEG ULCER

Computational Biology and Chemistry, Год журнала: 2024, Номер 111, С. 108112 - 108112

Опубликована: Май 27, 2024

Язык: Английский

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Synergizing GA-XGBoost and QSAR Modeling: Breaking Down Activity Cliffs in HDAC1 Inhibitors

Journal of Molecular Graphics and Modelling, Год журнала: 2024, Номер 135, С. 108915 - 108915

Опубликована: Дек. 20, 2024

Язык: Английский

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Identifying therapeutic target for prostate cancer: exploring Diosmetin as a CYP inhibitor

Discover Oncology, Год журнала: 2024, Номер 15(1)

Опубликована: Дек. 20, 2024

Язык: Английский

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