Computational exploration of FOXM1 inhibitors for glioblastoma: an integrated virtual screening and molecular dynamics simulation study

Journal of Biomolecular Structure and Dynamics, Год журнала: 2024, Номер unknown, С. 1 - 19

Опубликована: Фев. 2, 2024

In this study, a comprehensive investigation of set phytochemicals to identify potential inhibitors for the Forkhead box protein M1 (FOXM1) was conducted. FOXM1 is overexpressed in glioblastoma (GBM) cells and plays crucial role cell cycle progression, proliferation, invasion. have shown promising results preclinical studies, ongoing clinical trials are assessing their efficacy GBM patients. However, there limited studies on identification novel compounds against attractive therapeutic target. To address this, NPACT database containing 1,574 used, employing hierarchical multistep docking approach, followed by an estimation relative binding free energy. By fixing user-defined XP-dock MM-GBSA cut-off scores −6.096 −37.881 kcal/mol, chemical space further narrowed. Through exhaustive analysis molecular interactions various pharmacokinetics profiles, we identified four compounds, namely NPACT00002, NPACT01454, NPACT00856, NPACT01417, as inhibitors. assess stability protein-ligand dynamic conditions, 100 ns Molecular dynamics (MD) simulations were performed. Furthermore, mechanics with generalized Born surface area solvation (MM-GBSA) based energy estimations entire simulation trajectories revealed strong affinity all towards FOXM1, surpassing that control drug Troglitazone. Based extensively studied approaches, propose these molecules hold promise applications GBM. experimental validation will be necessary confirm targeted therapies.

Язык: Английский

In-silico and in-vitro evaluation of antifungal bioactive compounds from Streptomyces sp. strain 130 against Aspergillus flavus

Journal of Biomolecular Structure and Dynamics, Год журнала: 2024, Номер unknown, С. 1 - 19

Опубликована: Фев. 6, 2024

Streptomyces spp. are considered excellent reservoirs of natural bioactive compounds. The study evaluated the potential secondary metabolites from sp. strain 130 through PKS-I and NRPS gene-clusters screening. GC-MS analysis was done for metabolic profiling compounds in next set experiments. Identified antifungal underwent ADMET analyses to screen their toxicity. All compounds' molecular docking with structural gene products aflatoxin biosynthetic pathway Aspergillus flavus. MD simulations were utilized evaluate stability protein-ligand complexes under physiological conditions. Based on in-silico studies, compound 2,4-di-tert butyl-phenol (DTBP) selected in-vitro studies against Simultaneously, extracted two different solvents (ethyl-acetate methanol) used similar assays. MIC value DTBP found be 314 µg/mL, whereas ethyl-acetate extract methanol-extract, it 250 350 respectively. A mycelium growth assay analyze effect compounds/extracts formation In agar diffusion assay, zone inhibitions DTBP, extract, methanol observed diameters 11.3, 13.3, 7.6 mm, curve treated samples have delayed fungi, which signified that a fungistatic nature. Spot has determined fungal sensitivity sub-minimum inhibitory concentration study's results suggested can exploited antifungal-drug development.

Язык: Английский