In vitro antiamoebic activity of novel metronidazole derivatives and silver nanoparticle formulations against clinical isolates of Entamoeba histolytica

Amoebiasis caused by Entamoeba histolytica remains a major global health issue, with metronidazole treatment limited due to side effects and decreased efficacy. This study aimed to create novel metronidazole derivatives and silver nanoparticle formulations to potentially combat amoebic infections. Using in silico molecular docking, five derivatives (E1, E2, E4, E7, and E10) were designed and synthesized, with their structures confirmed via mass spectrometry and ¹H NMR.

Silver nanoparticles were produced using a green method and characterized through UV-Vis, FTIR, XRD, and FESEM, revealing spherical particles with sizes ranging from 29.54 to 53.48 nm. The docking results indicated that E1 had the strongest binding affinity against EhTrxR, followed by E7 and E10. In vitro testing showed that the derivatives, especially E10 combined with AgNPs, exhibited high trophozoite mortality (90%) after 48 hours, surpassing metronidazole alone (30%) and increasing up to 55% when combined with AgNPs.

E1 demonstrated the most activity in cyst assays, with mortality up to 75% at 40 minutes compared to 50% for metronidazole. Both the derivatives and metronidazole-AgNPs formulations showed increased anti-amoebic activity compared to their individual compounds, particularly E1 and its AgNPs formulations. However, more research is needed for therapeutic implications, including mechanism studies, toxicity studies, selectivity assays, and in vivo evaluation.

The study was conducted without funding and received ethical approval from the College of Applied Science – University of Fallujah.