Amoebiasis Revisited

  • Alka Mital


Amoebiasis, a disease characterized by abdominal pain, loose motion, and blood-containing feces, is caused by a unicellular protozoan parasite Entamoeba histolytica. It afflicts nearly 500 million people worldwide and is the second leading cause of death from a parasitic infection in children under 5 years of age. The cysts are the infective stages, and the infection spreads through ingestion of mature cysts in fecally contaminated food and drinking water or by hands from an infected person. A majority of infected persons often remain asymptomatic; however, in some cases, infection can lead to severe clinical complications like dysentery and amoebic liver abscesses. Though metronidazole (a 5-nitroimidazole) continues to be a drug of choice for the treatment of amoebic dysentery, for its complete cure, a combination of a tissue amoebicide (usually a 5-nitroimidazole) and a luminal amoebicide (e.g., diloxanide furoate) is required. Unfortunately, the occurrence of E. histolytica strains resistant to metronidazole, its potential carcinogenicity, and a strong metallic taste after a few days of use are some of its big limitations. Satranidazole, a novel 5-nitroimidazole discovered and developed in India, is now available in several formulations. Nevertheless, the treatment of amoebiasis continues to remain far from satisfactory, and there is a strong and compelling need to discover and develop novel and improved antiamoebic drugs. Further, the availability of clean drinking water, proper sanitation, and good personal hygiene including handwashing will continue to remain important driving factors in tackling the problem of amoebiasis. This overview summarizes the history, life cycle, currently available drugs, and, more importantly, the progress on the discovery of novel antiamoebic agents and various preventive measures for the control of amoebiasis.


Amoebiasis Entamoeba histolytica 5-nitroimidazoles Satranidazole 


  1. Abid M, Azam A (2006) Synthesis, characterization and antiamoebic activity of 1-(thiazolo[4,5-b]quinoxaline-2-yl)-3-phenyl-2-pyrazoline derivatives. Bioorg Med Chem Lett 16:2812–2816CrossRefGoogle Scholar
  2. Abid M, Husain K, Azam A (2005) Synthesis and antiamoebic activity of new oxime ether derivatives containing 2-acetylpyridine/2-acetylfuran. Bioorg Med Chem Lett 15:4375–4379CrossRefGoogle Scholar
  3. Abid M, Bhat AR, Athar F, Azam A (2009) Synthesis, spectral studies and antiamoebic activity of new 1-N-substituted thiocarbamoyl-3-phenyl-2-pyrazolines. Eur J Med Chem 44:417–425CrossRefGoogle Scholar
  4. Adagu IS, Nolder D, Warhurst DC, Rossignol JF (2002) In vitro activity of nitazoxanide and related compounds against isolates of Giardia intestinalis, Entamoeba histolytica and Trichomonas vaginalis. J Antimicrob Chemother 49:103–111CrossRefGoogle Scholar
  5. Ali V, Nozaki T (2007) Current therapeutics, their problems, and sulfur-containing-amino-acid metabolism as a novel target against infections by “amitochondriate” protozoan parasites. Clin Microbiol Rev 20:164–187CrossRefGoogle Scholar
  6. Aslam S, Musher DM (2007) Nitazoxanide: clinical studies of a broad-spectrum anti-infective agent. Future Microbiol 2:583–590CrossRefGoogle Scholar
  7. Athar F, Husain K, Abid M, Agarwal SM, Coles SJ, Hursthouse MB, Maurya MR, Azam A (2005) Synthesis and antiamoebic activity of gold (I), ruthenium (II) and copper (II) complexes of metronidazole. Chem Biodivers 2:1320–1330CrossRefGoogle Scholar
  8. Azam A, Agarwal SM (2007) Targeting Amoebiasis: status and developments. Current Bioactive compounds 3:121–133CrossRefGoogle Scholar
  9. Azam A, Peerzada MN, Ahmad K (2015) Parasitic diarrheal disease: drug development and targets. Front Microbiol 6:1–12CrossRefGoogle Scholar
  10. Bharti N, Shailendra, Coles SJ, Hursthouse MB, Mayer TA, Gonzalez Garza MT, Cruz-Vega DE, Mata-Cardenas BD, Naqvi F, Maurya MR, Azam A (2002) Synthesis, crystal structure and enhancement of the efficacy of metronidazole against Entamoeba histolytica by complexation with palladium (II), platinum (II) or copper (II). Helv Chim Acta 85:S2704–S2712CrossRefGoogle Scholar
  11. Bhat AR, Athar F, Azam A (2009a) Bis-pyrazolines: synthesis, characterization and antiamoebic activity as inhibitors of growth of Entamoeba histolytica. Eur J Med Chem 44:426–431CrossRefGoogle Scholar
  12. Bhat AR, Athar F, Azam A (2009b) New derivatives of 3,5-substituted-1,4,2-dioxazoles: synthesis and activity against Entamoeba histolytica. Eur J Med Chem 44:926–936CrossRefGoogle Scholar
  13. Budakoti A, Bhat AR, Athar F, Azam A (2008) Syntheses and evaluation of 3-(3-bromo phenyl)-5-phenyl-1-(thiazolo [4,5-b] quinoxaline-2-yl)-2-pyrazoline derivatives. Eur J Med Chem 43:1749–1757CrossRefGoogle Scholar
  14. Calzada F, Alanis AD, Meckes M, Tapia-Contreras A, Cedillo-Rivera R (1998) In vitro susceptibility of Entamoeba histolytica and Giardia lamblia to some medicinal plants used by the people of southern Mexico. Phytother Res 12:70–72CrossRefGoogle Scholar
  15. Calzada F, Velazquez C, Cedillo-Rivera R, Esquivel B (2003a) Antiprotozoal activity of the constituents of Teloxys graveolens. Phytother Res 17:731–732CrossRefGoogle Scholar
  16. Calzada F, Barbosa E, Cedillo-Rivera R (2003b) Antiamoebic activity of benzyl glucosinolate from Lepidium virginicum. Phytother Res 17:618–619CrossRefGoogle Scholar
  17. Campos-Rodriguezp R, Jarillo-Luna A (2005) The pathogenicity of Entamoeba histolytica is related to the capacity of evading innate immunity. Parasite Immunol 27:1–8CrossRefGoogle Scholar
  18. Chatterjee DK, Iyer SN, Venugopalan B, Raether W (1997) Antiamoebic activity of 3,3′-fluro-4,4′-di-(pyrrolidine-2-ylidene amino)-diphenyl (liroldine), against experimentally infected intestinal and hepatic amoebiasis. Indian J Exp Biol 35:765–770PubMedGoogle Scholar
  19. Debnath A, Parsonage D, Andrade RM, He C, Cobo ER, Hirata K, Chen S, García-Rivera G, Orozco E, Martínez MB, Gunatilleke SS, Barrios AM, Arkin MR, Poole LB, McKerrow JH, Reed SL (2012) A high-throughput drug screen for Entamoeba histolytica identifies a new lead and target. Nat Med 18:956–962CrossRefGoogle Scholar
  20. Diamond LS (1961) Axenic cultivation of Entamoeba histolytica. Science 134:336–337CrossRefGoogle Scholar
  21. Ghosh S, Chan JM, Lea CR, Meints GA, Lewis JC, Tovian ZS, Flessner RM, Loftus TC, Bruchhaus I, Kendrick H, Croft SL, Kemp RG, Kobayashi S, Nozaki T, Oldfield E (2004) Effects of bisphosphonates on the growth of Entamoeba histolytica and Plasmodium species in vitro and in vivo. J Med Chem 47:175–187CrossRefGoogle Scholar
  22. Hayat F, Azam A, Shin D (2016) Recent progress on the discovery of antiamoebic agents. Bioorg Med Chem Lett 26:5149–5159CrossRefGoogle Scholar
  23. Heredia RD, Fonseca JA, López MC (2012) Entamoeba moshkovskii perspectives of a new agent to be considered in the diagnosis of amoebiasis. Acta Trop 123:139CrossRefGoogle Scholar
  24. Hung CC (2007) Amoebiasis: current status in Australia. Med J Aust 187:372PubMedGoogle Scholar
  25. Hung CC, Dar-Der Ji HYS, Lee YT, Hsu SY, Chang SY, Wu CH, Chan YH, Hsiao CF, Liu WC, Colebunders R (2008) Increased risk for Entamoeba histolytica infection and invasive Amebiasis in HIV seropositive men who have sex with men in Taiwan. PLoS Negl Trop Dis 2:e175CrossRefGoogle Scholar
  26. Husain K, Abid M, Azam A (2008) Novel Pd (II) complexes of 1-N-substituted 3-phenyl-2-pyrazoline derivatives and evaluation of antiamoebic activity. Eur J Med Chem 43:393–403CrossRefGoogle Scholar
  27. Imperato PJ (1981) A historical overview of amebiasis. Bull N Y Acad Med 57:175–187PubMedPubMedCentralGoogle Scholar
  28. Legator MS, Connor TH, Stoeckel M (1975) Detection of mutagenic activity of metronidazole and niridazole in body fluids of humans and mice. Science 188:1118–1119CrossRefGoogle Scholar
  29. Leitsch D, Kolarich D, Wilson IB, Altmann F, Duchene M (2007) Nitroimidazole action in Entamoeba histolytica: a central role for thioredoxin reductase. PLoS Biol 5:e211CrossRefGoogle Scholar
  30. Lopez-Vallejo F, Medina-Franco JL, Hernandez-Campos A, Rodrıguez-Morales S, Yepez L, Cedillo R, Castillo R (2007) Molecular modeling of some 1H-benzimidazole derivatives with biological activity against Entamoeba histolytica: a comparative molecular field analysis study. Bioorg Med Chem 15:1117–1126CrossRefGoogle Scholar
  31. Marshall SJ, Russell PF, Wright CW, Anderson MM, Phillipson JD, Kirby GC, Warhurst DC, Schiff PL Jr (1994) In vitro antiplasmodial, antiamoebic, and cytotoxic activities of a series of bisbenzylisoquinoline alkaloids. Antimicrob Agents Chemother 38:96–103CrossRefGoogle Scholar
  32. Ordaz-Pichardo C, Shibayama M, Villa-Trevino S, Arriaga-Alba M, Angeles E, de la Garza M (2005) Antiamoebic and toxicity studies of a carbamic acid derivative and its therapeutic effect in a hamster model of hepatic amoebiasis. Antimicrob Agents Chemother 49:1160–1168CrossRefGoogle Scholar
  33. Orozco E, Lopez C, Gomez C, Perez DG, Marchat L, Banuelos C, Delgadillo DM (2002) Multidrug resistance in the protozoan parasite Entamoeba histolytica. Parasitol Int 51:353–359CrossRefGoogle Scholar
  34. Peterson KM, Singh U, Petri WA Jr (2011) Enteric Amoebiasis. In: Guerrant R, Walker DH, Weller PF (eds) Tropical infectious diseases: principles, pathogens and practice, 3rd edn. Saunders Elsevier, Philadelphia, p 614CrossRefGoogle Scholar
  35. Petri WA Jr (2003) Therapy of intestinal protozoa. Trends Parasitol 19:523–526CrossRefGoogle Scholar
  36. Roder C, Thomson MJ (2015) Auranofin: repurposing an old drug for a golden new age. Drugs in R & D 15:13–20CrossRefGoogle Scholar
  37. Rogers L (1912) The rapid cure of amoebic dysentery and hepatitis by hypodermic injections of soluble salts of emetine. Br Med J 1:14–24CrossRefGoogle Scholar
  38. Rossignol JF, Kabil SM, El-Gohary Y, Younis AM (2007) Nitazoxanide in the treatment of amoebiasis. Trans R Soc Trop Med Hyg 101:1025–1031CrossRefGoogle Scholar
  39. Rustia M, Shubik P (1972) Induction of lung tumors and malignant lymphomas in mice by metronidazole. J Natl Cancer Inst 48:721–729PubMedGoogle Scholar
  40. Seifert K, Duchene M, Wernsdorfer WH, Kollaritsch H, Scheiner O, Wiedermann G, Hottkowitz T, Eibl H (2001) Effects of miltefosine and other alkylphosphocholines on human intestinal parasite Entamoeba histolytica. Antimicrob Agents Chemother 45:1505–1510CrossRefGoogle Scholar
  41. Sharma P, Sharma JD (2001) A review of plant species assessed in vitro for antiamoebic activity or both antiamoebic and antiplasmodial properties. Phytother Res 15:1–17CrossRefGoogle Scholar
  42. Sharma S, Athar F, Maurya MR, Azam A (2005a) Copper (II) complexes with substituted thiosemicarbazones of thiophene-2-carboxaldehyde: synthesis, characterization and antiamoebic activity against E. histolytica. Eur J Med Chem 40:1414–1419CrossRefGoogle Scholar
  43. Sharma S, Athar F, Maurya MR, Naqvi F, Azam A (2005b) Novel bidentate complexes of Cu (II) derived from 5-nitrofuran-2-carboxaldehyde thiosemicarbazones with antiamoebic activity against Entamoeba histolytica. Eur J Med Chem 40:557–562CrossRefGoogle Scholar
  44. Singh S, Husain K, Athar F, Azam A (2005a) Synthesis and antiamoebic activity of 3,7-dimethyl-pyrazolo[3,4-e][1,2,4]triazin-4-yl thiosemicarbazide derivatives. Eur J Med Chem 25:255–262Google Scholar
  45. Singh S, Athar F, Azam A (2005b) Synthesis, spectral studies and in vitro assessment for antiamoebic activity of new cyclooctadiene ruthenium (II) complexes with 2-nitrothiophene-2-carboxaldehyde thiosemicarbazones. Bioorg Med Chem Lett 15:5424–5428CrossRefGoogle Scholar
  46. Singh S, Athar F, Maurya MR, Azam A (2006) Cyclooctadiene Ru (II) complexes of thiophene-2-carboxaldehyde-derived thiosemicarbazones: synthesis, characterization and antiamoebic activity. Eur J Med Chem 41:592–598CrossRefGoogle Scholar
  47. Singh S, Bharti N, Mohapatra PP (2009) Chemistry and biology of synthetic and naturally occurring Antiamoebic agents. Chem Rev 109:1900–1947CrossRefGoogle Scholar
  48. Stanley SL Jr (2003) Amoebiasis. Lancet 361:1025–1034CrossRefGoogle Scholar
  49. Stanley SL Jr (2006) Vaccines for amoebiasis: barriers and opportunities. Parasitology 133:81–86CrossRefGoogle Scholar
  50. Venugopalan B, Patel B, Karnik PJ, de Souza NJ, Chatterjee DK, Iyer N (1996) Synthesis of diphenyl bisamidines as potential amoebicides. Eur J Med Chem 1:485–488CrossRefGoogle Scholar
  51. Wassermann C, Hellberg A, Tannich E, Bruchhaus I (1999) Metronidazole resistance in the protozoan parasite Entamoeba histolytica is associated with increased expression of iron-containing superoxide dismutase and peroxiredoxin and decreased expression of ferredoxin 1 and flavin reductase. J Biol Chem 274:26051–26056CrossRefGoogle Scholar
  52. Wright CW, Phillipson JD (1990) Natural products and the development of selective antiprotozoal drugs. Phytother Res 4:127–139CrossRefGoogle Scholar
  53. Wright CW, Bray DH, O’Neill MJ, Warhurst DC, Phillipson JD, Quetin Leclercq J, Angenot L (1991) Antiamoebic and antiplasmodial activities of alkaloids isolated from Strychnos usambarensis. Planta Med 57:337–340CrossRefGoogle Scholar

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© Springer Nature Singapore Pte Ltd. 2018

Authors and Affiliations

  • Alka Mital
    • 1
  1. 1.Department of Medicinal ChemistryNational Institute of Pharmaceutical Education and ResearchS. A. S. NagarIndia

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