کاربردهای شیمی تجزیه
Somayeh Farahmand; Mobina Ashtari; Reza Haji Hosseini; Gholamreza Bakhshi Khaniki
Abstract
Hepatitis B virus (HBV) infection remains a global health challenge, and mutations in the core antigen (HBcAg) can compromise the efficacy of current antiviral therapies. This study aimed to identify potential natural and FDA-approved compounds targeting wild-type (WPr) and P135Q mutant (MPr) HBcAg using ...
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Hepatitis B virus (HBV) infection remains a global health challenge, and mutations in the core antigen (HBcAg) can compromise the efficacy of current antiviral therapies. This study aimed to identify potential natural and FDA-approved compounds targeting wild-type (WPr) and P135Q mutant (MPr) HBcAg using a comprehensive in silico approach. Natural compounds were filtered using Lipinski's Rule of Five and ADMET profiling. Molecular docking was performed using AutoDock Vina (version 1.2.x, 2021), and the top-ranked complexes were subjected to 500 ns molecular dynamics simulations using GROMACS 2023 with the AMBER99SB force field. Structural and energetic analyses included RMSD, RMSF, radius of gyration (Rg), solvent-accessible surface area (SASA), hydrogen bonding, principal component analysis (PCA), and MM/PBSA binding free energy calculations. Among 5,000 screened phytochemicals, Carnosic acid (Csa) and Nordentatin (Nor) demonstrated favorable binding affinities (ΔG = −8.85 and −9.84 kcal/mol, respectively) with acceptable ADMET profiles. MD simulations revealed distinct binding mechanisms: Csa stabilized WPr through electrostatic interactions, while Nor stabilized MPr through persistent hydrogen bonds and van der Waals contacts involving Trp102, Ser106, and Tyr118. Binding free energy analysis suggested that Csa may have stronger affinity for the mutant form, whereas Nor appeared to favor the wild-type. The P135Q mutation significantly influenced ligand binding dynamics and interaction patterns, highlighting the structural differences between wild-type and mutant HBcAg. Our computational findings suggest that Csa and Nor may serve as potential candidates for HBcAg binding. However, these predictions are purely computational and require experimental validation to confirm their actual biological activity.
Sholeh Javadi; Somayeh Farahmand; Helia Bayat; Reza HajiHosseini; Sima Nasri
Abstract
Triple-negative breast cancer (TNBC) lacks targetable receptors, rendering conventional chemotherapy the sole standard of care despite its associated toxicity and acquired resistance. The constitutively activated NF-κB and STAT3 signaling axes represent mechanistically interdependent oncogenic ...
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Triple-negative breast cancer (TNBC) lacks targetable receptors, rendering conventional chemotherapy the sole standard of care despite its associated toxicity and acquired resistance. The constitutively activated NF-κB and STAT3 signaling axes represent mechanistically interdependent oncogenic drivers in TNBC, making their simultaneous inhibition a compelling therapeutic strategy. β-Sitosterol, the predominant phytosterol of Allium cepa seeds, has demonstrated broad antiproliferative properties; however, its capacity for dual-target engagement against NFKB1 and STAT3 has not been systematically characterized. GC–MS profiling of A. cepa seed oil identified β-sitosterol as the principal constituent (80.45%). Computational ADMET analysis, Human Protein Atlas-based immunocytochemical target validation, and Auto Dock Vina molecular docking against NFKB1 (PDB: 5AX3) and STAT3 (PDB: 7LET) were performed. Anticancer activity was evaluated in MDA-MB-231 cells via MTT assay, with apoptotic mechanism characterized by Annexin V-FITC/PI flow cytometry. β-Sitosterol demonstrated favorable drug-likeness with predicted mitochondrial localization and absence of mutagenicity. Docking yielded binding energies of −7.0 and −6.7 kcal/mol for STAT3 and NFKB1, respectively, driven by hydrophobic interactions. MTT assay revealed concentration-dependent cytotoxicity (IC₅₀ = 39.56 µM; 72 h; F = 113.8, p < 0.0001). Flow cytometry confirmed significant induction of early (30.7 ± 2.5%) and late apoptosis (20.3 ± 4.4%) versus negligible baseline levels in controls. β-Sitosterol exhibits dual computational binding affinity for NFKB1 and STAT3 alongside potent pro-apoptotic activity in TNBC cells, establishing a mechanistic foundation for its further translational development.
