Nylton Ferreira Maciel, Gleice VasconcelosPereira do Lago, Glauce Vasconcelos da Silva Pereira, Ingryd Nayara de Farias Ramos, Aline Costa Bastos, Igor Alexandre Rocha Barreto, Nathiel Sarges Moraes, Marcos NazarenoLauné dos Santos, João Augusto Pereira da Rocha, Alencar Kolinski Machado, Waldomiro Paschoal, Márcio Marcelo da Silva Pessoa, Maria de Nazaré Maciel Uesugi, André Salim Khayat, J. Ribeiro Cruz, José de ArimatéiaRodrigues do Rêgo, Maria Regina Sarkis Peixoto Joele, Davi do Socorro Barros Brasil
ABSTRACT The green synthesis of silver nanoparticles (AgNPs) offers an environmentally friendly alternative to conventional methods by replacing toxic chemical reagents with natural sources. These methods utilize microorganisms, such as bacteria and fungi, or natural plant extracts rich in secondary metabolites that act as reducing and stabilizing agents during nanoparticle formation. In this study, we biosynthesized AgNPs using an ethanolic extract of Piper nigrum seeds and isolated piperine (PPN), the main bioactive compound. Furthermore, we evaluated the cytotoxic properties of PPN and its interaction with AgNPs (Np‐AgPPN) in gastric cancer cells. The samples were characterized using UV–visible (UV–Vis) spectroscopy, Fourier transform infrared (FTIR), scanning electron microscopy with energy‐dispersive x‐ray spectroscopy (SEM–EDS), x‐ray diffraction (XRD), thermogravimetric (TG), and differential scanning calorimetry (DSC). Results suggest successful functionalization of AgNPs with piperine (Np‐AgPPN). UV–Vis spectroscopy showed a hypsochromic shift of the maximum peak and a hypochromic effect, suggesting electronic interactions between PPN and Ag. FTIR‐attenuated total reflectance (ATR) spectra revealed shifts in the carbonyl and aromatic bands, confirming PPN–Ag complex formation. SEM micrographs displayed rectangular crystals characteristic of PPN, whereas Np‐AgPPN exhibited amorphous clusters. XRD analysis revealed a decrease in crystallinity and peaks characteristic of metallic Ag. Thermal analyses (TG/DTG and DSC) demonstrated the reduced thermal stability of Np‐AgPPN compared to PPN, in addition to altered endothermic and exothermic transitions. In vitro cytotoxicity assays showed that Np‐AgPPN had superior antitumor activity compared to PPN, with IC 50 in the range 23.1–33.9 µg/mL, particularly against the gastric cell line AGP01 PIWIL1 − / − . These results demonstrate that piperine‐functionalized AgNPs can be synthesized from a piperine‐rich extract and that Np‐AgPPN exhibits superior cytotoxic effects against gastric cancer cells. In conclusion, this work highlights the feasibility of producing piperine‐functionalized AgNPs through a green synthesis approach and demonstrates their enhanced cytotoxic activity against gastric cancer cells, reinforcing the therapeutic potential of this strategy.