Parasitology Research

, Volume 114, Issue 4, pp 1249–1261 | Cite as

Natural and synthetic compound anti-Trichomonas vaginalis: an update review

  • Patrícia de Brum Vieira
  • Raquel Brandt Giordani
  • Alexandre José Macedo
  • Tiana TascaEmail author


Trichomonas vaginalis is a flagellate protozoan that causes trichomonosis, a sexually transmitted disease of worldwide importance. However, the infection has long received much less attention than other parasitic and sexually transmitted diseases. This negligence leads to poor diagnosis and underestimated prevalence values, and consequently, it has been associated to increasing acquisition and transmission of HIV, pregnancy outcomes, infertility, pelvic inflammatory disease, and cervical and prostate cancer. In view of increased resistance to drugs belonging to the nitroimidazole class, new treatment alternatives are urgently needed. Natural products provide an immeasurable wealth of active molecules, and a great number of new drugs have been originated from these compounds. In addition, new synthetic products or derivatives from old drugs also provide an alternative to treat trichomonosis. Albeit many studies have been performed with natural products against T. vaginalis, none of them progressed to clinical trials. Overall, inadequate financial investments are made, and no alternative treatment for trichomonosis has been discovered; meanwhile, hundreds of thousands of people will remain infected and suffering the serious consequences of this nonviral STD. Thus, it is highlighted that clinical trials for better understanding the potential in vitro are necessary and urgent in order to furnish a new therapeutic alternative for trichomonosis treatment. The current review attempts to give an overview on the potential of natural and synthetic products as antitrichomonal.


Anti-protozoan Anti-Trichomonas vaginalis activity Metronidazole derivatives Natural products Synthetic compounds Trichomonosis 



P.B.V. thanks CAPES for student scholarship A.J.M and T.T. thank CNPq for researcher fellowship and for financial NANOBIOTEC-Brasil (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, CAPES). Authors thank the Post-Graduation Program in Pharmaceutical Sciences, UFRGS.


  1. Aldrete MEC, Salgado-Zamora H, Luna J, Melendez E, Meraz-Rios MA (2005) A high-throughput colorimetric and fluorometric microassay for the evaluation of nitroimidazole derivatives anti-trichomonas activity. Toxicol In Vitro 19:1045–1050. doi: 10.1016/j.tiv.2005.04.007 CrossRefGoogle Scholar
  2. Andrzejewska M, Yepez-Mulia L, Tapia A, Cedillo-Rivera R, Laudy AE, Starościak BJ, Kazimierczuk Z (2004) Synthesis, and antiprotozoal and antibacterial activities of S-substituted 4,6-dibromo- and 4,6-dichloro-2-mercaptobenzimidazoles. Eur J Pharm Sci 21:323–329. doi: 10.1016/j.ejps.2003.10.024 CrossRefPubMedGoogle Scholar
  3. Arthan D, Sithiprom S, Thima K, Limmatvatirat C, Chavalitshewinkoon-Petmitr P, Svasti J (2008) Inhibitory effects of Thai plants beta-glycosides on Trichomonas vaginalis. Parasitol Res 103:443–448. doi: 10.1007/s00436-008-0996-2 CrossRefPubMedGoogle Scholar
  4. Bala V et al (2014) Design and synthesis of substituted morpholin/piperidin-1-yl-carbamodithioates as promising vaginal microbicides with spermicidal potential. Bioorg Med Chem Lett 24:5782–5786. doi: 10.1016/j.bmcl.2014.10.040 CrossRefPubMedGoogle Scholar
  5. Brandelli CLC, Vieira PB, Macedo AJ, Tasca T (2013) Remarkable anti-Trichomonas vaginalis activity of plants traditionally used by the Mbya-Guarani indigenous group in Brazil. Biomed Res Int 2013:7. doi: 10.1155/2013/826370 CrossRefGoogle Scholar
  6. Bruno M, Bancheva S, Rosselli S, Maggio A (2013) Sesquiterpenoids in subtribe Centaureinae (Cass.) Dumort (tribe Cardueae, Asteraceae): Distribution, 13C NMR spectral data and biological properties. Phytochemistry 95:19–93. doi: 10.1016/j.phytochem.2013.07.002 CrossRefPubMedGoogle Scholar
  7. Calzada F, Yepez-Mulia L, Tapia-Contreras A (2007) Effect of Mexican medicinal plant used to treat trichomoniasis on Trichomonas vaginalis trophozoites. J Ethnopharmacol 113:248–251. doi: 10.1016/j.jep.2007.06.001 CrossRefPubMedGoogle Scholar
  8. Cano PA, Islas-Jacome A, Gonzalez-Marrero J, Yepez-Mulia L, Calzada F, Gamez-Montano R (2014) Synthesis of 3-tetrazolylmethyl-4H-chromen-4-ones via Ugi-azide and biological evaluation against Entamoeba histolytica, Giardia lamblia and Trichomonas vaginalis. Bioorg Med Chem 22:1370–1376. doi: 10.1016/j.bmc.2013.12.069 CrossRefPubMedGoogle Scholar
  9. Cargnin ST et al (2013) Anti-Trichomonas vaginalis activity of Hypericum polyanthemum extract obtained by supercritical fluid extraction and isolated compounds. Parasitol Int 62:112–117. doi: 10.1016/j.parint.2012.10.006 CrossRefPubMedGoogle Scholar
  10. Cheikh-Ali Z, Adiko M, Bouttier S, Bories C, Okpekon T, Poupon E, Champy P (2011) Composition, and antimicrobial and remarkable antiprotozoal activities of the essential oil of rhizomes of Aframomum sceptrum K. Schum. (Zingiberaceae). Chem Biodivers 8:658–667. doi: 10.1002/cbdv.201000216 CrossRefPubMedGoogle Scholar
  11. Coro J et al (2005) Synthesis and antiprotozoan evaluation of new alkyl-linked bis(2-thioxo-[1,3,5]thiadiazinan-3-yl) carboxylic acids. Bioorg Med Chem 13:3413–3421. doi: 10.1016/j.bmc.2005.03.009 CrossRefPubMedGoogle Scholar
  12. Crowell AL, Sanders-Lewis KA, Secor WE (2003) In vitro metronidazole and tinidazole activities against metronidazole-resistant strains of Trichomonas vaginalis. Antimicrob Agents Chemother 47:1407–1409CrossRefPubMedCentralPubMedGoogle Scholar
  13. Damke E et al (2013) Spermicidal and anti-Trichomonas vaginalis activity of Brazilian Sapindus saponaria. BMC Complement Altern Med 13:196. doi: 10.1186/1472-6882-13-196 CrossRefPubMedCentralPubMedGoogle Scholar
  14. De Villiers BJ, Van Vuuren SF, Van Zyl RL, Van Wyk BE (2010) Antimicrobial and antimalarial activity of Cussonia species (Araliaceae). J Ethnopharmacol 129:189–196. doi: 10.1016/j.jep.2010.02.014 CrossRefPubMedGoogle Scholar
  15. Desrivot J, Waikedre J, Cabalion P, Herrenknecht C, Bories C, Hocquemiller R, Fournet A (2007) Antiparasitic activity of some New Caledonian medicinal plants. J Ethnopharmacol 112:7–12. doi: 10.1016/j.jep.2007.01.026 CrossRefPubMedGoogle Scholar
  16. Ertabaklar H, Kivcak B, Mert T, Ozensoy Toz S (2009) In vitro activity of Arbutus unedo leaf extracts against Trichomonas vaginalis trophozoites. Türkiye Parazitol Derg 33:263–265PubMedGoogle Scholar
  17. Frasson AP et al (2012) First report of anti-Trichomonas vaginalis activity of the medicinal plant Polygala decumbens from the Brazilian semi-arid region, Caatinga. Parasitol Res 110:2581–2587. doi: 10.1007/s00436-011-2787-4 CrossRefPubMedGoogle Scholar
  18. Giordani RB et al (2010) Candimine-Induced Cell Death of the Amitochondriate Parasite Trichomonas vaginalis. J Nat Prod 73:2019–2023. doi: 10.1021/np100449g CrossRefPubMedGoogle Scholar
  19. Giordani RB, Araújo DP, Duarte M, Zuanazzi JA, Tasca T, De Almeida MV (2011a) Anti-protozoal activity of diamine derivatives. Biomed Pharmacother 65:60–62. doi: 10.1016/j.biopha.2010.10.006 CrossRefPubMedGoogle Scholar
  20. Giordani RB et al (2011b) Lycorine induces cell death in the amitochondriate parasite, Trichomonas vaginalis, via an alternative non-apoptotic death pathway. Phytochemistry 72:645–650. doi: 10.1016/j.phytochem.2011.01.023 CrossRefPubMedGoogle Scholar
  21. Giordani RB, Junior COR, de Andrade JP, Bastida J, Zuanazzi JAS, Tasca T, de Almeida MV (2012) Lycorine Derivatives Against Trichomonas vaginalis. Chem Biol Drug Des 80:129–133. doi: 10.1111/j.1747-0285.2012.01333.x CrossRefPubMedGoogle Scholar
  22. Goodhew EB, Secor WE (2013) Drug library screening against metronidazole-sensitive and metronidazole-resistant Trichomonas vaginalis isolates. Sex Transm Infect 89:479–484. doi: 10.1136/sextrans-2013-051032 CrossRefPubMedGoogle Scholar
  23. Hassani S, Asghari G, Yousefi H, Kazemian A, Rafieiean M, Darani HY (2013) Effects of different extracts of Eucalyptus camaldulensis on Trichomonas vaginalis parasite in culture medium. Adv Biomed Res 2:47. doi: 10.4103/2277-9175.114187 CrossRefPubMedCentralPubMedGoogle Scholar
  24. Hernández-Núñez E et al (2009) Synthesis and in vitro trichomonicidal, giardicidal and amebicidal activity of N-acetamide(sulfonamide)-2-methyl-4-nitro-1H-imidazoles. Eur J Med Chem 44:2975–2984. doi: 10.1016/j.ejmech.2009.01.005 CrossRefPubMedGoogle Scholar
  25. Hui X, Desrivot J, Bories C, Loiseau PM, Franck X, Hocquemiller R, Figadère B (2006) Synthesis and antiprotozoal activity of some new synthetic substituted quinoxalines. Bioorg Med Chem Lett 16:815–820. doi: 10.1016/j.bmcl.2005.11.025 CrossRefPubMedGoogle Scholar
  26. Innocente AM, Vieira PB, Frasson AP, Casanova BB, Gosmann G, Gnoatto SCB, Tasca T (2014) Anti-Trichomonas vaginalis activity from triterpenoid derivatives. Parasitol Res 113:2933–2940 doi: 10.1007/s00436-014-3955-0
  27. Kumar L et al (2010) Imidazole derivatives as possible microbicides with dual protection. Eur J Med Chem 45:817–824. doi: 10.1016/j.ejmech.2009.10.021 CrossRefPubMedGoogle Scholar
  28. Kumar L et al (2013) Azole-carbodithioate hybrids as vaginal anti-Candida contraceptive agents: design, synthesis and docking studies. Eur J Med Chem 70:68–77. doi: 10.1016/j.ejmech.2013.09.007 CrossRefPubMedGoogle Scholar
  29. Lara-Diaz VJ et al (2009) Microbiological and toxicological effects of Perla black bean (Phaseolus vulgaris L.) extracts: in vitro and in vivo studies. Basic Clin Pharmacol Toxicol 104:81–86. doi: 10.1111/j.1742-7843.2008.00330.x CrossRefPubMedGoogle Scholar
  30. Mallo N, Lamas J, Leiro JM (2013) Hydrogenosome metabolism is the key target for antiparasitic activity of resveratrol against Trichomonas vaginalis. Antimicrob Agents Chemoter 57:2476–2484. doi: 10.1128/aac. 00009-13 CrossRefGoogle Scholar
  31. Mayer AMS, Hamann MT (2005) Marine pharmacology in 2001–2002: Marine compounds with anthelmintic, antibacterial, anticoagulant, antidiabetic, antifungal, anti-inflammatory, antimalarial, antiplatelet, antiprotozoal, antituberculosis, and antiviral activities; affecting the cardiovascular, immune and nervous systems and other miscellaneous mechanisms of action. Comp Biochem Physiol, Part C: Toxicol Pharmacol 140:265–286. doi: 10.1016/j.cca.2005.04.004 Google Scholar
  32. Moon T, Wilkinson JM, Cavanagh HM (2006) Antiparasitic activity of two Lavandula essential oils against Giardia duodenalis, Trichomonas vaginalis and Hexamita inflata. Parasitol Res 99:722–728. doi: 10.1007/s00436-006-0234-8 CrossRefPubMedGoogle Scholar
  33. Moo-Puc R, Robledo D, Freile-Pelegrin Y (2008) Evaluation of selected tropical seaweeds for in vitro anti-trichomonal activity. J Ethnopharmacol 120:92–97. doi: 10.1016/j.jep.2008.07.035 CrossRefPubMedGoogle Scholar
  34. Moo-Puc JA, Martin-Quintal Z, Miron-Lopez G, Moo-Puc RE, Quijano L, Mena-Rejon GJ (2014) Isolation and antitrichomonal activity of the chemical constituents of the leaves of Maytenus phyllanthoides Benth. (Celastraceae). Quim Nova 37:85–U114CrossRefGoogle Scholar
  35. Muzny CA, Schwebke JR (2013) The clinical spectrum of Trichomonas vaginalis infection and challenges to management. Sex Transm Infect 89:423–425. doi: 10.1136/sextrans-2012-050893 CrossRefPubMedGoogle Scholar
  36. Naidoo D, van Vuuren SF, van Zyl RL, de Wet H (2013) Plants traditionally used individually and in combination to treat sexually transmitted infections in northern Maputaland, South Africa: Antimicrobial activity and cytotoxicity. J Ethnopharmacol 149:656–667. doi: 10.1016/j.jep.2013.07.018 CrossRefPubMedGoogle Scholar
  37. Navarrete-Vázquez G et al (2006) Synthesis and antiprotozoal activity of some 2-(trifluoromethyl)-1H-benzimidazole bioisosteres. Eur J Med Chem 41:135–141. doi: 10.1016/j.ejmech.2005.09.001 CrossRefPubMedGoogle Scholar
  38. Newman DJ, Cragg GM (2012) Natural products as sources of new drugs over the 30 years from 1981 to 2010. J Nat Prod 75:311–335. doi: 10.1021/np200906s CrossRefPubMedCentralPubMedGoogle Scholar
  39. Ngo LT, Okogun JI, Folk WR (2013) 21st century natural product research and drug development and traditional medicines. Nat Prod Rep 30:584–592. doi: 10.1039/c3np20120a CrossRefPubMedCentralPubMedGoogle Scholar
  40. Ofer K, Gold D, Flescher E (2008) Methyl jasmonate induces cell cycle block and cell death in the amitochondriate parasite Trichomonas vaginalis. Int J Parasitol 38:959–968. doi: 10.1016/j.ijpara.2007.12.008 CrossRefPubMedGoogle Scholar
  41. Petrin D, Delgaty K, Bhatt R, Garber G (1998) Clinical and microbiological aspects of Trichomonas vaginalis. Clin Microbiol Rev 11:300–317PubMedCentralPubMedGoogle Scholar
  42. Poole DN, McClelland RS (2013) Global epidemiology of Trichomonas vaginalis. Sex Transm Infect 89:418–422. doi: 10.1136/sextrans-2013-051075 CrossRefPubMedGoogle Scholar
  43. Potdar D, Hirwani RR, Dhulap S (2012) Phyto-chemical and pharmacological applications of Berberis aristata. Fitoterapia 83:817–830. doi: 10.1016/j.fitote.2012.04.012 CrossRefPubMedGoogle Scholar
  44. Raj R, Singh P, Haberkern NT, Faucher RM, Patel N, Land KM, Kumar V (2013) Synthesis of 1H-1,2,3-triazole linked beta-lactam-isatin bi-functional hybrids and preliminary analysis of in vitro activity against the protozoal parasite Trichomonas vaginalis. Eur J Med Chem 63:897–906. doi: 10.1016/j.ejmech.2013.03.019 CrossRefPubMedGoogle Scholar
  45. Robinson SC (1962) Trichomonal vaginitis resistant to metranidazole. Can Med Assoc J 86:665PubMedCentralPubMedGoogle Scholar
  46. Rocha TD, Vieira PB, Gnoatto SC, Tasca T, Gosmann G (2012) Anti-Trichomonas vaginalis activity of saponins from Quillaja, Passiflora, and Ilex species. Parasitol Res 110:2551–2556. doi: 10.1007/s00436-011-2798-1 CrossRefPubMedGoogle Scholar
  47. Schwebke JR, Barrientes FJ (2006) Prevalence of Trichomonas vaginalis isolates with resistance to metronidazole and tinidazole. Antimicrob Agents Chemother 50:4209–4210. doi: 10.1128/aac. 00814-06 CrossRefPubMedCentralPubMedGoogle Scholar
  48. Scopel M, dos Santos O, Frasson AP, Abraham W-R, Tasca T, Henriques AT, Macedo AJ (2013) Anti-Trichomonas vaginalis activity of marine-associated fungi from the South Brazilian Coast. Exp Parasitol 133:211–216. doi: 10.1016/j.exppara.2012.11.006 CrossRefPubMedGoogle Scholar
  49. Secor WE, Meites E, Starr MC, Workowski KA (2014) Neglected parasitic infections in the United States: trichomoniasis. Am J Trop Med Hyg 90:800–804. doi: 10.4269/ajtmh. 13-0723 CrossRefPubMedCentralPubMedGoogle Scholar
  50. Sena AC et al (2007) Trichomonas vaginalis infection in male sexual partners: implications for diagnosis, treatment, and prevention. Clin Infect Dis 44:13–22. doi: 10.1086/511144 CrossRefPubMedGoogle Scholar
  51. Sena AC et al (2012) Chlamydia trachomatis, Mycoplasma genitalium, and Trichomonas vaginalis infections in men with nongonococcal urethritis: predictors and persistence after therapy. J Infect Dis 206:357–365. doi: 10.1093/infdis/jis356 CrossRefPubMedCentralPubMedGoogle Scholar
  52. Soria-Arteche O et al (2013) Synthesis and antiprotozoal activity of nitazoxanide–N-methylbenzimidazole hybrids. Bioorg Med Chem Lett 23:6838–6841. doi: 10.1016/j.bmcl.2013.10.011 CrossRefPubMedGoogle Scholar
  53. Sutcliffe S, Neace C, Magnuson NS, Reeves R, Alderete JF (2012) Trichomonosis, a common curable STI, and prostate carcinogenesis - a proposed molecular mechanism. PLoS Pathog 8:e1002801. doi: 10.1371/journal.ppat.1002801 CrossRefPubMedCentralPubMedGoogle Scholar
  54. Swygard H, Seña AC, Hobbs MM, Cohen MS (2004) Trichomoniasis: clinical manifestations, diagnosis and management. Sex Transm Infect 80:91–95. doi: 10.1136/sti.2003.005124 CrossRefPubMedCentralPubMedGoogle Scholar
  55. Tiwari P, Singh D, Singh MM (2008) Anti-Trichomonas activity of Sapindus saponins, a candidate for development as microbicidal contraceptive. J Antimicrob Chemoth 62:526–534. doi: 10.1093/jac/dkn223 CrossRefGoogle Scholar
  56. Torres-Gómez H et al (2008) Design, synthesis and in vitro antiprotozoal activity of benzimidazole-pentamidine hybrids. Bioorg Med Chem Lett 18:3147–3151. doi: 10.1016/j.bmcl.2008.05.009 CrossRefPubMedGoogle Scholar
  57. Valdez-Padilla D, Rodríguez-Morales S, Hernández-Campos A, Hernández-Luis F, Yépez-Mulia L, Tapia-Contreras A, Castillo R (2009) Synthesis and antiprotozoal activity of novel 1-methylbenzimidazole derivatives. Bioorgan Med Chem 17:1724–1730. doi: 10.1016/j.bmc.2008.12.059 CrossRefGoogle Scholar
  58. van Vuuren SF, Naidoo D (2010) An antimicrobial investigation of plants used traditionally in southern Africa to treat sexually transmitted infections. J Ethnopharmacol 130:552–558. doi: 10.1016/j.jep.2010.05.045 CrossRefPubMedGoogle Scholar
  59. Vilela R, Menna-Barreto RFS, Benchimol M (2010) Methyl jasmonate induces cell death and loss of hydrogenosomal membrane potential in Trichomonas vaginalis. Parasitol Int 59:387–393. doi: 10.1016/j.parint.2010.05.003 CrossRefPubMedGoogle Scholar
  60. Vital PG, Rivera WL (2011) Antimicrobial activity, cytotoxicity, and phytochemical screening of Voacanga globosa (Blanco) Merr. leaf extract (Apocynaceae). Asian Pac J Trop Med 4:824–828. doi: 10.1016/s1995-7645(11)60202-2 CrossRefPubMedGoogle Scholar
  61. Wachter B, Syrowatka M, Obwaller A, Walochnik J (2014) In vitro efficacy of curcumin on Trichomonas vaginalis. Wien Klin Wochenschr. doi: 10.1007/s00508-014-0522-8 PubMedGoogle Scholar
  62. WHO (2012) Global incidence and prevalence of selected curable sexually transmitted infections: 2008: World Health Organization, Department of Reproductive Health and Research, 2012 ISBN 978 92 4 150383 9 Reproductive health matters 20:207-209Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Patrícia de Brum Vieira
    • 1
  • Raquel Brandt Giordani
    • 2
  • Alexandre José Macedo
    • 3
  • Tiana Tasca
    • 1
    Email author
  1. 1.Laboratório de Pesquisa em Parasitologia, Faculdade de FarmáciaUniversidade Federal do Rio Grande do SulPorto AlegreBrasil
  2. 2.Centro de Ciências da Saúde, Departamento de FarmáciaUniversidade Federal do Rio Grande do NorteNatalBrasil
  3. 3.Faculdade de Farmácia e Centro de BiotecnologiaUniversidade Federal do Rio Grande do SulPorto AlegreBrasil

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