Neisseria gonorrhoeae, the causative agent of gonorrhoea, represents a major global health challenge due to increasing antimicrobial resistance (AMR) and the absence of an effective vaccine. The rapid emergence of resistance to all currently available antibiotics has led the World Health Organization to classify N. gonorrhoeae as a high-priority pathogen, highlighting the urgent need for alternative therapeutic strategies. Natural products and their derivatives offer a structurally diverse platform for antimicrobial discovery, although their clinical translation is often hindered by poor solubility and limited bioavailability.
In this study, we investigated the antibacterial activity of four synthetic gibbilimbol B analogues, both individually and in combination with silver nanoparticles (AgNPs), against N. gonorrhoeae strains. Gibbilimbol analogues (esters and amides with saturated or unsaturated side chains) were synthesized and structurally characterised, while AgNPs were prepared via chemical reduction and stabilised with polyvinylpyrrolidone. The resulting analogue–AgNP mixtures were confirmed to be stable by UV–Vis spectroscopy and transmission electron microscopy, showing spherical nanoparticles (10–15 nm) with preserved morphology.
Individually, gibbilimbol analogues exhibited moderate bactericidal activity (MBC₅₀: 6.25–25 µM; MBC₉₀: 25–50 µM), whereas AgNPs demonstrated substantially higher potency (MBC₅₀: 0.19 µM; MBC₉₀: 0.78 µM), outperforming ceftriaxone under the assay conditions. Importantly, combinations of gibbilimbol analogues with sub-effective concentrations of AgNPs significantly enhanced bactericidal activity compared to either component alone. Notably, mixtures containing unsaturated analogues (compounds 2 and 4) showed statistically significant increases in bacterial killing (p < 0.05 and p < 0.01, respectively), exceeding predicted additive effects and suggesting potential synergistic interactions.
These findings indicate that combining natural product-inspired molecules with nanomaterials can enhance antimicrobial efficacy against N. gonorrhoeae. The observed structure-dependent enhancement further suggests that unsaturation in the alkyl side chain may facilitate interactions with AgNPs, improving delivery or activity.
Overall, this study provides the first evidence that gibbilimbol analogue–AgNP hybrid systems offer a promising strategy for the development of new anti-gonococcal agents. Further mechanistic and toxicity studies are warranted to advance these combinations towards clinical application.