Anti-Trichomonas vaginalis activity of ursolic acid derivative: a promising alternative
- 152 Downloads
Trichomonas vaginalis is an extracellular parasite that binds to the epithelium of the human urogenital tract and causes the sexually transmitted infection, trichomoniasis. In view of increased resistance to drugs belonging to the 5-nitroimidazole class, new treatment alternatives are urgently needed. In this study, eight semisynthetized triterpene derivatives were evaluated for in vitro anti-T. vaginalis activity. Ursolic acid and its derivative, 3-oxime-urs-12-en-28-oic-ursolic acid (9), presented the best anti-T. vaginalis activity when compared to other derivatives, with minimum inhibitory concentration (MIC) at 25 μM. Moreover, 9 was active against several T. vaginalis fresh clinical isolates. Hemolysis assay demonstrated that 9 presented a low hemolytic effect. Importantly, 25 μM 9 was not cytotoxic against the Vero cell lineage. Finally, we demonstrated that compound 9 acts synergistically with metronidazole against a T. vaginalis metronidazole-resistant isolate. This report reveals the high potential of the triterpenoid derivative 9 as trichomonicidal agent.
KeywordsTriterpenes Trichomonas vaginalis Ursolic acid Betulinic acid Synthetic derivatives
The authors thank LRNANO/CNANO for the NMR analysis.
This work received financial support from REDE NANOBIOTEC-CAPES/Brazil (grant 23038.019022/2009-68), CNPq/Brazil (grant 474930/2012-2), and INCT-IF. Patrícia B. Vieira receives scholarship from CAPES; Tiana Tasca received researcher fellowship (grant 307447/2014-6) from CNPq.
Compliance with ethical standards
The Universidade Federal do Rio Grande do Sul Research Ethical Committee approved documents, procedures, and project under authorization CAAE 47423415.5.0000.5347 and 18923. The informed consent for each participant was approved by the Institutional Review Board.
Conflict of interest
The authors declare that they have no conflict of interest.
- Bache M, Zschornak MP, Passin S, Kessler J, Wichmann H, Kappler M, Paschke R, Kaluderovic GN, Kommera H, Taubert H, Vordermark D (2011) Increased betulinic acid induced cytotoxicity and radiosensitivity in glioma cells under hypoxic conditions. Radiat Oncol 6:111. https://doi.org/10.1186/1748-717X-6-111 CrossRefPubMedPubMedCentralGoogle Scholar
- Butler SE, Augostini P, Secor WE (2010) Mycoplasma hominis infection of Trichomonas vaginalis is not associated with metronidazole-resistant trichomoniasis in clinical isolates from the United States. Parasitol Res 107:1023–1027. https://doi.org/10.1007/s00436-010-1975-y CrossRefPubMedGoogle Scholar
- Gauthier C, Legault J, Girard-Lalancette K, Mshvildadze V, Pichette A (2009) Haemolytic activity, cytotoxicity and membrane cell permeabilization of semi-synthetic and natural lupane- and oleanane-type saponins. Bioorg Med Chem 17:2002–2008. https://doi.org/10.1016/j.bmc.2009.01.022 CrossRefPubMedGoogle Scholar
- Silva GN, Maria NR, Schuck DC, Cruz LN, de Moraes MS, Nakabashi M, Graebin C, Gosmann G, Garcia CR, Gnoatto SC (2013) Two series of new semisynthetic triterpene derivatives: differences in anti-malarial activity, cytotoxicity and mechanism of action. Malar J 12:89. https://doi.org/10.1186/1475-2875-12-89 CrossRefPubMedPubMedCentralGoogle Scholar
- Silva GN, Schuck DC, Cruz LN, Moraes MS, Nakabashi M, Gosmann G, Garcia CR, Gnoatto SC (2015) Investigation of antimalarial activity, cytotoxicity and action mechanism of piperazine derivatives of betulinic acid. Tropical Med Int Health 20:29–39. https://doi.org/10.1111/tmi.12395 CrossRefGoogle Scholar
- Twu O, Dessi D, Vu A, Mercer F, Stevens GC, de Miguel N, Rappelli P, Cocco AR, Clubb RT, Fiori PL, Johnson PJ (2014) Trichomonas vaginalis homolog of macrophage migration inhibitory factor induces prostate cell growth, invasiveness, and inflammatory responses. PNAS 111:8179–8184. https://doi.org/10.1073/pnas.1321884111 CrossRefPubMedPubMedCentralGoogle Scholar