Sesquiterpene lactones and the diterpene 5-epi-icetexone affect the intracellular and extracellular stages of Trypanosoma cruzi

Lozano, Esteban; Barrera, Patricia; Salinas, Romina; Vega, Israel A.; Nieto, Matı́as; Tonn, Carlos E.; Kemmerling, Ulrike; Mortara, Renato Arruda; Sosa, Miguel A. Gama

doi:10.1016/j.parint.2012.06.005

Cited by 17 publications

(22 citation statements)

References 29 publications

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“…These results are in line with those reported by Lozano et al [10] who have found trypomastigotes to be highly sensitive to ICTX.…”

Section: Accepted Manuscriptsupporting

confidence: 93%

“…In addition, the search for drugs for the chronic phase has been hindered by the lack of animal models reproducing the human disease. However, some experimental models employing animal cell lines have been successful [9,10] as well as models employing mice maintained under controlled experimental conditions [9,[11][12][13][14], which are being used to study the mechanism of infection, the survival of intracellular parasites and the evolution of the disease. For decades, numerous natural or synthetic compounds have proved to be active against T. cruzi, albeit a successful therapy for Chagas' disease is still lacking, since important side effects have been observed in patients treated with these compounds [4,15].…”

Section: Accepted Manuscriptmentioning

confidence: 99%

“…epimastigotes [17] and the infective forms of the parasite (trypomastigotes and intracellular amastigotes), and with low cytotoxicity on the host's cells [10]. It is possible that the deleterious effect on parasites was due to an oxidative action of the compound through the quinone groups [17].…”

Section: Accepted Manuscriptmentioning

confidence: 99%

“…ACCEPTED MANUSCRIPT 6 However, effects of this terpenoid on the other phases of the infection, that is, tissue invasion and multiplication, cannot be ruled out, since ICTX has also been found to be active against the intracellular forms of the parasite [10]. Although the mechanism of action of ICTX also remains to be determined, the generation of an oxidative stress status has been proposed [20].…”

Section: Accepted Manuscriptmentioning

confidence: 99%

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The in vivo trypanocidal effect of the diterpene 5-epi-icetexone obtained from Salvia gilliesii

Lozano

Strauss

Spina

et al. 2016

Parasitology International

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The search for new compounds with trypanocidal activity is crucial for the treatment of Chagas' disease. Previous in vitro studies have shown that the diterpene 5-epi-icetexone (ICTX) is active against Trypanosoma cruzi. The aim of this work was to evaluate the effect of ICTX on the parasites in infected mice, in an experimental model that mimics the acute phase of the disease. Swiss albino mice were infected with T. cruzi and treated daily with 10mg/kg/day ICTX (i.p.). Infected mice and mice injected with either saline or the vehicle DMSO were used as controls. Animals' survival and parasitemia were monitored once a week and histological studies were made at necropsy by the 5th week after infection. It was observed that the administration of ICTX increased the survival of mice infected, and induced a significant decrease in the parasitemia, as compared to controls. A similar protective effect was observed when animals were treated orally with benznidazole (BZN, used as a control of antiparasitic effect). By the 5th week post-infection, the presence of amastigote nests was observed within the fibers of the cardiac and skeletal muscle in controls, but not in animals treated with either ICTX or BZN. In addition, inflammatory infiltrates were observed in the tissues of controls, but not in animals treated with the drugs. We conclude that ICTX has an antiparasitic effect against T. cruzi, thus constituting an interesting option for the treatment of Chagas' disease, alone or combined with other drugs.

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“…These results are in line with those reported by Lozano et al [10] who have found trypomastigotes to be highly sensitive to ICTX.…”

Section: Accepted Manuscriptsupporting

confidence: 93%

Section: Accepted Manuscriptmentioning

confidence: 99%

Section: Accepted Manuscriptmentioning

confidence: 99%

Section: Accepted Manuscriptmentioning

confidence: 99%

See 2 more Smart Citations

The in vivo trypanocidal effect of the diterpene 5-epi-icetexone obtained from Salvia gilliesii

Lozano

Strauss

Spina

et al. 2016

Parasitology International

View full text Add to dashboard Cite

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“…Lozano et al 44,45 reported a more triterpenoid resistence against trypomastigote forms may be related with their non-multiplying capacity. Despite the low antitrypomastigote activity, these compounds are promising candidates for therapeutic targets in the chronic stage.…”

Section: Discussionmentioning

confidence: 99%

Anti-Trypanosoma Activity and Synergistic Effects of Natural and Semi-Synthetic Triterpenes and Predominant Cell Death through Autophagy in Amastigote Forms

Bossolani

Ueda-Nakamura

Silva

et al. 2017

J. Braz. Chem. Soc.

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Chagas' disease is a parasitic disease with unsatisfactory treatment, mainly in chronic stage. This study aimed to evaluate the trypanocidal activity and action mechanisms of α/β-amyrin and its semisynthetic derivatives, together with four isolated natural triterpenes, tested against trypomastigote and amastigote forms. The structure-activity relationship was suggested and cytotoxicity was measured. In general, greater polar compounds may have improved the selectivity to the protozoan. Action mechanisms were only performed for the amastigotes of Trypanosoma cruzi by evaluating the ultrastructural alterations, membrane permeability, mitochondrial membrane potential and cell volume, since the majority of compounds displayed promising antiamastigote activities. Triterpenes promoted changes on mitochondrial membrane potential and ultrastructural features that suggest autophagy processes. Both combinations between α/β-amyrin and 3-O-acetyl-11-oxo-α/β-amyrin and 3-O-acetyl-α/β-amyrin with benznidazole displayed synergistic effects against amastigotes and antagonistic effects on LLCMK 2 cells. The antiamastigote activities, chemical derivatization, drug combinations and action mechanisms revealed to be crucial approaches toward this chronic disease.

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Diterpenes as lead molecules against neglected tropical diseases

et al. 2016

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Nowadays, neglected tropical diseases (NTDs) are reported to be present everywhere. Poor and developing areas in the world have received great attention to NTDs. Drug resistance, safety profile, and various challenges stimulate the search for alternative medications. Plant-based drugs are viewed with great interest, as they are believed to be devoid of side effects. Diterpenes, a family of essential oils, have showed attractive biological effects. A systematic review of the literature was carried out to summarize available evidences of diterpenes against NTDs. For this, databases were searched using specific search terms. Among the 2338 collected reports, a total of 181 articles were included in this review. Of them, 148 dealt with investigations using single organisms, and 33 used multiple organisms. No mechanisms of action were reported in the case of 164 reports. A total of 93.92% were related to nonclinical studies, and 4.42% and 1.66% dealt with preclinical and clinical studies, respectively. The review displays that many diterpenes are effective upon Chagas disease, chikungunya, echinococcosis, dengue, leishmaniasis, leprosy, lymphatic filariasis, malaria, schistosomiasis, and tuberculosis. Indeed, diterpenes are amazing drug candidates against NTDs. Copyright © 2016 John Wiley & Sons, Ltd.

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Sesquiterpene lactones and the diterpene 5-epi-icetexone affect the intracellular and extracellular stages of Trypanosoma cruzi

Cited by 17 publications

References 29 publications

The in vivo trypanocidal effect of the diterpene 5-epi-icetexone obtained from Salvia gilliesii

The in vivo trypanocidal effect of the diterpene 5-epi-icetexone obtained from Salvia gilliesii

Anti-Trypanosoma Activity and Synergistic Effects of Natural and Semi-Synthetic Triterpenes and Predominant Cell Death through Autophagy in Amastigote Forms

Diterpenes as lead molecules against neglected tropical diseases

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