Green Synthesis of Piper nigrum Copper-based Nanoparticles: In-Silico Study and ADMET Analysis to Assess Their Antioxidant, Antibacterial, and Cytotoxic Effects

Abstract Nano-biotechnology gained popularity and interest among scientists since it allowed for the green manufacturing of nanoparticles by employing plants as reducing agents. This method was safe, cheap, reproducible, and eco-friendly. In this study, the therapeutic potential of Piper nigrum fruit was mixed with the antibacterial activity of metallic copper to produce copper nanoparticles. The synthesis of copper nanoparticles was indicated by a colour change from brown to blue. Physical characterisation of PN-CuNPs was done by using UV-vis spectroscopy, FTIR, SEM, EDX, XRD and Zeta analyser. PN-CuNPs exhibited potential antioxidant, antibacterial and cytotoxic activities. PN-CuNPs showed improved free radical scavenging activity in a concentration dependant manner, reaching a maximum of 92%, 90% and 86% with DPPH, H 2 O 2 and PMA tests. The antibacterial zone of inhibition of PN-CuNPs was the highest against S. aureus (23 mm) and the lowest against E. coli (10 mm), respectively. In vitro cytotoxicity of PN-CuNPs was demonstrated against MCF-7 breast cancer cell lines. The green synthesis of P. nigrum fruit was an excellent approach to produce PN-CuNPs with significant biological properties. Furthermore, more than 50 components of Piper nigrum extract were selected and subjected to in-silico molecular docking using the C-Docker protocol in the binding pockets of glutathione reductase, E. coli DNA gyrase topoisomerase II and EGFR tyrosine to discover their druggability. Pipercyclobutanamide A (26), pipernigramide F (32) and pipernigramide G (33) scored the best Gibbs free energy 50.489, 51.9306, 58.615 Kcal/mol, respectively. The ADMET/TOPKAT analysis confirmed the favourable pharmacokinetics, pharmacodynamics and toxicity profiles of the three promising compounds.