Research Outputs
aMulti-target in silico profiling of silymarin derivatives against oncogenic pathways: Integration of docking, DFT, ADMET, and molecular dynamics
Silymarin derivatives, renowned for their antioxidant and hepatoprotective properties, have recently emerged as promising candidates for anticancer therapy due to their potential to modulate critical oncogenic pathways. Four silymarin derivatives (silibinin, isosilibinin, silicristin, silidianin), known for liver protection, were explored as potential multi-target anticancer agents using computational methods. Molecular docking against key cancer proteins (AKT, PI3K, PARP, mTOR, GSK3-β, PDK1, PAK4) identified silicristin as the strongest binder, confirmed by stable molecular dynamics simulations and favorable binding energy (ΔG = −125.78 kcal/mol via MM-GBSA). Silidianin showed the highest chemical reactivity (smallest HOMO–LUMO gap: 0.1535 eV). All compounds displayed promising ADMET profiles: high intestinal absorption, low blood-brain barrier penetration, and silidianin exhibited the lowest acute toxicity (LD50 = 10,000 mg/kg). While potential immunotoxicity was noted, silicristin and silidianin emerged as the most promising candidates due to their strong target binding, stability, reactivity, and favorable safety predictions, warranting further experimental validation. This multi-scale computational study identifies silicristin and silidianin as promising multi-target anticancer candidates. Their stability, favorable electronic profiles, and low predicted toxicity support further in vitro and in vivo validation.
A computational study of the antioxidant power of eugenol compared to Vitamin C
The antioxidant power of eugenol and vitamin C was examined by analyzing the ability of these ligands to bind to the NADPH oxidase protein target and evaluating their bond interactions with critical residues. The results confirm that docked ligands are more stable in the specified active region of 2CDU during a MD simulation of 100 ns and 2CDU protein-ligand interactions with docked ligands showed significant hydrogen bond, hydrophobic, and water bridge formation. Eugenol exhibits hydrogen bond interactions with critical residues in the selective pocket in comparison to vitamin C. Also, eugenol had a similar binding orientation and very considerable stability in the selective pocket of 2CDU with a high binding energy with lipophilic energy. The electrostatic potential maps indicate that for eugenol, the –OH and –OCH3 sites, while that the –OH and –CO functional groups in vitamin C are responsible of the antioxidant activities of these compounds. HAT and SET mechanisms suggest that eugenol may become a better antioxidant than vitamin C.
Theoretical investigation of the molecular structure and molecular docking of etoricoxib
In this work, a computational chemical study of Etoricoxib was carried out at the X/6311G(d,p) (where X=B3LYP, M06 and B97XD) level of theory, at the gas, aqueous and ethanol phases. Through the chemical reactivity descriptors derived from the DFT, it was possible to find that Etoricoxib structure exhibits a major chemical activity in water and ethanol phases in comparison to the gas phase, which suggests this drug would be more active in biological solvents like in blood, tissues and places where the ciclooxigenasa 2 (COX)-2 is found. In addition, a molecular docking analysis was conducted to study the interaction of Etoricoxib with the COX-2 active site. The results suggest that Etoricoxib interacts with 19 amino acid residues inside the COX-2 active site.