Green Synthesis of Fenugreek-Mediated Silver Nanoparticles with Potent Antioxidant, Antimicrobial, and Selective Cytotoxic Effects against MCF-7 Breast Cancer Cells: Experimental and in Silico Insight

Shahad Basil Ismael

Abstract

Fenugreek (Trigonella frenum-graecum), a traditional medicinal herb rich in bioactive phytochemicals, has attracted considerable attention for its antioxidant and anticancer properties. In this study, a green synthesis approach was developed to produce silver nanoparticles (AgNPs) using aqueous fenugreek leaf extract and evaluated their antioxidant, antimicrobial and cytotoxic effects against breast cancer cell (MCF-7). Antioxidant potential was conformed through total phenolic and flavonoid content, reducing power, and DPPH radical scavenging assays, with fenugreek extract showing strong activity compared to standard. The formation of AgNPs was validated by UV-Vis spectroscopy(surface plasmon resonance peak at ~418), fourier-tansform infrared spectroscopy (FTIR) indicating involvement of hydroxyl and carbonyl groups in reduction/capping, and atomic force microscopy(AFM) revealing nanoscale particle size(62-80nm). The green-synthesized AgNPs exhibited significant antibacterial and antifungal activity, with inhibition zones of up to 33 mm against Pseudomonas aeruginosa and 42mm against Candida albicans. Cytotoxicity assays on MCF-7 cells demonstrated dose-dependent effects, with an IC₅₀ of 112.4µg/mL while normal fibroblasts (HdFn) remained comparatively less affected (IC₅₀= 140.4), suggesting selective toxicity. To complement these findings, molecular docking was performed for three major fenugreek phytochemicals-diosgenin, quercetin, and trigonelline against breast cancer relevant proteins (ERꭤ , EGFR, and BCL-2). Diosgenin and quercetin exhibited strong binding affinities (-8.6 to -9.2 kcal/mol), indicating potential apoptotic and antiproliferative mechanisms underlying the observed cytotoxicity. Together, the results highlights foenum-graecum mediated AgNPs as a promising biogenic nanoplatform with potent antioxidant, antimicrobial, and anticancer activities, warranting further in vivo validation for breast cancer therapy.