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<p>Amoebiasis from <i>Entamoeba histolytica</i> continues to be a significant global health problem, and treatment with metronidazole is limited due to adverse effects and loss of efficacy. The objectives of this study were to design, synthesise and evaluate novel metronidazole derivatives along with their respective silver nanoparticle AgNP formulations as potential anti-amoebic agents. Molecular docking in silico against <i>E. histolytica</i> thioredoxin reductase (EhTrxR) was employed to develop five derivatives (E1, E2, E4, E7 and E10), which were synthesized and then structurally confirmed by mass spectrometry (MS) and ¹H nuclear magnetic resonance (¹H NMR). Silver nanoparticles were synthesised by the green method and characterised through UV-Vis, FTIR, XRD and FESEM, indicating spherical particles with sizes between 29.54 and 53.48&#xa0;nm. In the docking results, among the tested derivatives, E1 showed the strongest predicated binding affinity against EhTrxR, with an energy score of − 10.40&#xa0;kcal/mol, followed by E7 and E10. The binding affinity of E1 was also notably stronger than that of E2 and E4, indicating its more favourable based interaction with target enzyme. The derivatives exhibited a very effective anti-amoebic activity in vitro, particularly when combined with AgNPs. At 48&#xa0;h, the highest trophozoite mortality (90%) was observed for E10 + AgNPs, followed by E7 + AgNPs (73%), in comparison to metronidazole alone which demonstrated only 30% and increased up to 55% when combined with AgNPs. In cyst assays E1 had the most activity, with mortality up to 75% at 40&#xa0;min compared with 50% for metronidazole. All treatments exhibited significant dose- and time-dependent effects (<i>p</i> &lt; 0.001). Both novel metronidazole derivatives and the metronidazole-AgNPs formulations exhibit increased anti-amoebic activity over their corresponding compounds alone, particularly E1 and its AgNPs formulations results which could be a first step towards the identification of anti-amoebic leads but still no therapeutic implications can be drawn without carrying out mechanism studies, toxicity studies, selectivity assays and in vivo evaluation.</p>

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

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  • 发表日期：

    2026年8月2日

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  • Abdelrahman Essam Alawi,
  • Anas Abdullah Hamad

摘要

Amoebiasis from Entamoeba histolytica continues to be a significant global health problem, and treatment with metronidazole is limited due to adverse effects and loss of efficacy. The objectives of this study were to design, synthesise and evaluate novel metronidazole derivatives along with their respective silver nanoparticle AgNP formulations as potential anti-amoebic agents. Molecular docking in silico against E. histolytica thioredoxin reductase (EhTrxR) was employed to develop five derivatives (E1, E2, E4, E7 and E10), which were synthesized and then structurally confirmed by mass spectrometry (MS) and ¹H nuclear magnetic resonance (¹H NMR). Silver nanoparticles were synthesised by the green method and characterised through UV-Vis, FTIR, XRD and FESEM, indicating spherical particles with sizes between 29.54 and 53.48 nm. In the docking results, among the tested derivatives, E1 showed the strongest predicated binding affinity against EhTrxR, with an energy score of − 10.40 kcal/mol, followed by E7 and E10. The binding affinity of E1 was also notably stronger than that of E2 and E4, indicating its more favourable based interaction with target enzyme. The derivatives exhibited a very effective anti-amoebic activity in vitro, particularly when combined with AgNPs. At 48 h, the highest trophozoite mortality (90%) was observed for E10 + AgNPs, followed by E7 + AgNPs (73%), in comparison to metronidazole alone which demonstrated only 30% and increased up to 55% when combined with AgNPs. In cyst assays E1 had the most activity, with mortality up to 75% at 40 min compared with 50% for metronidazole. All treatments exhibited significant dose- and time-dependent effects (p < 0.001). Both novel metronidazole derivatives and the metronidazole-AgNPs formulations exhibit increased anti-amoebic activity over their corresponding compounds alone, particularly E1 and its AgNPs formulations results which could be a first step towards the identification of anti-amoebic leads but still no therapeutic implications can be drawn without carrying out mechanism studies, toxicity studies, selectivity assays and in vivo evaluation.