Flutamide

Li N, et al. Bioorganic Chemistry, 2025, 160, 108479.

This study investigates the binding mechanisms of Flutamide, a non-steroidal anti-androgen drug, with bovine serum albumin (BSA), employing a comprehensive experimental and theoretical approach. Fluorescence quenching experiments demonstrated a static quenching mechanism, with Flutamide reducing the intrinsic fluorescence of BSA. UV-visible absorption spectroscopy confirmed the formation of the BSA-Flutamide complex, and binding site analysis revealed a 1:1 stoichiometry, indicating a single binding site. Thermodynamic parameters were extracted using Van't Hoff analysis, highlighting the role of hydrophobic interactions and hydrogen bonding in complex formation. Circular dichroism spectroscopy was applied to assess conformational changes in BSA upon Flutamide binding, indicating minor secondary structural alterations. Molecular docking studies revealed that Flutamide preferentially occupies a hydrophobic pocket within BSA, stabilized by hydrogen bonds with key amino acid residues. Finally, 100 ns molecular dynamics simulations validated the stability of the BSA-Flutamide complex under physiological conditions, showing minimal structural deviations.

Hosseini S. F., et al. Tissue and Cell, 2025, 94, 102807.

This study explored the application of Flutamide, a nonsteroidal antiandrogen, in combination with resveratrol to enhance therapeutic outcomes in prostate cancer cell models. LNCaP (androgen-sensitive), DU145, and PC3 (androgen-insensitive) cell lines were used to simulate disease progression stages. The MTT assay established IC₅₀ values for both agents. Annexin-V/PI staining quantified apoptosis, while PI staining assessed DNA cell cycle distribution. Apoptosis- and metastasis-related gene expression (BAX, BCL-2, VEGFC, HIF-1α, Snail1, E-Cadherin, KLK3) was quantified by real-time PCR.
Functional assays, including scratch-wound migration, colony formation, Hoechst 33342 nuclear staining, and 3D spheroid formation, demonstrated that the Flutamide-resveratrol combination suppressed migration, reduced proliferation, and promoted apoptosis, even in androgen-refractory lines. Mechanistically, co-treatment significantly upregulated pro-apoptotic BAX and epithelial marker E-Cadherin while downregulating BCL-2, VEGFC, and EMT driver Snail1. KLK3 suppression indicated reduced prostate-specific signaling.

Bagherzadeh Z, et al. Journal of Molecular Graphics and Modelling, 2025, 140, 109084.

A density functional theory (DFT) investigation has been employed to evaluate the potential of pristine and alkali metal-encapsulated B40 fullerenes as molecular sensors for the anticancer drug flutamide.
In this computational experiment, the interaction of flutamide with B40, Na@B40, and K@B40 was analyzed through adsorption energy calculations, dipole moment evaluation, HOMO-LUMO energy gap changes, and thermodynamic descriptors. Adsorption energies for flutamide on M@B40 structures were found to be approximately -3.2 kcal/mol, indicating moderate physisorption. These interactions were characterized as exothermic and spontaneous, consistent in both gas and aqueous media.
Dipole moment analysis revealed an increase upon drug adsorption, suggesting heightened polarity and sensitivity of the system. Moreover, flutamide adsorption led to a decrease in the energy band gap by 9% for B40 and 3% for Na@B40, inferring improved electrical conductivity-a critical parameter for sensor signal transduction.

Nematollahi D, et al. Electrochimica Acta, 2024, 502, 144741.

In a recent investigation, flutamide, a nonsteroidal antiandrogen drug, was subjected to late-stage modification (LSMD) via electrochemical synthesis to generate novel derivatives with enhanced antibacterial properties. This study utilized a successive paired electrochemical (SPE) approach, employing flutamide as the substrate and arylsulfinic acids or barbituric acids as nucleophiles.
For the synthesis of sulfonamide derivatives (SU1-SU4), an undivided cell was filled with a mixture of phosphate buffer (pH 3.0, 0.2 M)/acetonitrile (50:50 v/v, 80 mL) containing flutamide (0.5 mmol) and equimolar arylsulfinic acid. Electrolysis was performed under a constant current density of 1.2 mA cm⁻² (25 mA) for 3 hours and 20 minutes, corresponding to a total charge of 300 C.
Similarly, for spiroderivative synthesis (SP1-SP3), phosphate buffer (pH 6.0, 0.2 M)/acetonitrile (50:50 v/v, 80 mL) with flutamide (0.5 mmol) and barbituric acid (1.0 mmol) underwent electrolysis at 0.9 mA cm⁻² (19 mA) for 5 hours and 50 minutes, delivering 400 C. Upon completion, the electrolytic mixture was refrigerated overnight, facilitating the precipitation of products, which were collected by filtration and washed thoroughly with distilled water.

Hosseinpour M, et al. Separation and Purification Technology, 2025, 355(B), 129705.

This study explores the electrocatalytic degradation of flutamide (FLU), an anti-prostate cancer drug, employing a simple graphite/β-PbO₂ (G/β-PbO₂) electrode. The experimental design focused on achieving high degradation efficiencies through a convergent-paired strategy, particularly by reducing the nitro group in FLU's metabolite, 4-nitro-3-(trifluoromethyl) aniline (NTA). Electrochemical experiments were conducted at an optimized pH of 5.0, pollutant concentration of 138 ppm, and an applied current density of 4.9 mA/cm². Under these conditions, the G/β-PbO₂ electrode exhibited impressive stability (>60 hours) and delivered high degradation efficiencies: 86% for FLU and 99% for NTA individually, and 82% and 92%, respectively, when both pollutants coexisted. The study also comprehensively analyzed the electrochemical behavior of FLU and NTA, revealing distinct reaction mechanisms and adsorption-diffusion characteristics.