Activity of Gibbilimbol Analogues Combined with Silver Nanoparticles Against Neisseria gonorrhoeae

Abstract Neisseria gonorrhoeae is the causative agent of gonorrhea, one of the most common sexually transmitted infections globally. Due to its increasing resistance to available antibiotics, it has been classified by the World Health Organization as a high-priority pathogen for the development of new antimicrobial strategies. In this context, natural products represent a valuable source of structurally diverse bioactive compounds and continue to serve as an inspiration for antibacterial discovery. However, their clinical application is often limited by poor solubility and low bioavailability. The incorporation of nanomaterials such as silver nanoparticles (AgNPs) has emerged as a promising strategy to overcome these limitations and improve the biological performance of natural product-based systems. In this study, combinations of gibbilimbol B analogues with AgNPs were prepared and evaluated for their in vitro bactericidal activity against N. gonorrhoeae. The individual compounds exhibited moderate bactericidal activity and low cytotoxicity toward mammalian cells, whereas combinations with AgNPs enhanced antibacterial efficacy. At the tested concentrations, the combination of AgNPs with analogue 4 showed a bactericidal effect significantly greater than the combined effect expected from the individual components, supporting a synergistic interaction under this specific experimental condition. Furthermore, the individual compounds, AgNPs, and selected AgNP–gibbilimbol analogue combinations retained bactericidal activity against antimicrobial-resistant gonococcal isolates from the CDC/FDA collection. This is the first study to combine gibbilimbol analogues with AgNPs and evaluate the bactericidal activity of these mixtures, highlighting the potential of such combinations as a novel antibacterial strategy against drug-resistant N. gonorrhoeae.