Antiparasitic effect of (−)-α-bisabolol against Trypanosoma cruzi Y strain forms

Menezes, Ramon Róseo Paula Pessoa Bezerra de; Sampaio, Tiago Lima; Lima, Dânya Bandeira; Sousa, Paloma Leão; Azevedo, Isabella Evelyn Prado de; Magalhães, Emanuel Paula; Tessarolo, Louise Donadello; Marinho, Márcia Machado; Santos, Ricardo; Martins, Alice Maria Costa

doi:10.1016/j.diagmicrobio.2019.06.012

Cited by 26 publications

(15 citation statements)

References 48 publications

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“…Nevertheless, studies using benznidazole and derivatives present results with lower ROS production in 24 h when compare with results demonstrated in this work. Therefore, DETC present an interesting result in ROS production against different strains of T. cruzi corroborating with other authors those use compounds with capacity of stimulate ROS production [55][56][57] .…”

Section: Discussionsupporting

confidence: 89%

Insights of antiparasitic activity of sodium diethyldithiocarbamate against different strains of Trypanosoma cruzi

Oliveira

Torres

Moreno

et al. 2021

Sci Rep

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Chagas disease is caused by Trypanosoma cruzi and affects thousands of people. Drugs currently used in therapy are toxic and have therapeutic limitations. In addition, the genetic diversity of T. cruzi represents an important variable and challenge in treatment. Sodium diethyldithiocarbamate (DETC) is a compound with pharmacological versatility acting as metal chelators and ROS generation. Thus, the objective was to characterize the antiparasitic action of DETC against different strains and forms of T. cruzi and their mechanism. The different strains of T. cruzi were grown in LIT medium. To evaluate the antiparasitic activity of DETC, epimastigote and trypomastigote forms of T. cruzi were used by resazurin reduction methods and by counting. Different response patterns were obtained between the strains and an IC50 of DETC ranging from 9.44 ± 3,181 to 60.49 ± 7.62 µM. Cell cytotoxicity against 3T3 and RAW cell lines and evaluated by MTT, demonstrated that DETC in high concentration (2222.00 µM) presents low toxicity. Yet, DETC causes mitochondrial damage in T. cruzi, as well as disruption in parasite membrane. DETC has antiparasitic activity against different genotypes and forms of T. cruzi, therefore, representing a promising molecule as a drug for the treatment of Chagas disease.

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Section: Discussionsupporting

confidence: 89%

Insights of antiparasitic activity of sodium diethyldithiocarbamate against different strains of Trypanosoma cruzi

Oliveira

Torres

Moreno

et al. 2021

Sci Rep

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“…The results indicate that with increased reactive oxygen species, compound 7 induces oxidative stress on the parasite. Thus, flow cytometry analysis was performed to verify the ability of compound 7 to change T. cruzi parameters [35].…”

Section: Resultsmentioning

confidence: 99%

Trypanocidal Mechanism of Action and in silico Studies of p-Coumaric Acid Derivatives

Lopes

Castillo

Monteiro

et al. 2019

IJMS

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Trypanosoma species are responsible for chronic and systemic infections in millions of people around the world, compromising life quality, and family and government budgets. This group of diseases is classified as neglected and causes thousands of deaths each year. In the present study, the trypanocidal effect of a set of 12 ester derivatives of the p-coumaric acid was tested. Of the test derivatives, pentyl p-coumarate (7) (5.16 ± 1.28 μM; 61.63 ± 28.59 μM) presented the best respective trypanocidal activities against both epimastigote and trypomastigote forms. Flow cytometry analysis revealed an increase in the percentage of 7-AAD labeled cells, an increase in reactive oxygen species, and a loss of mitochondrial membrane potential; indicating cell death by necrosis. This mechanism was confirmed by scanning electron microscopy, noting the loss of cellular integrity. Molecular docking data indicated that of the chemical compounds tested, compound 7 potentially acts through two mechanisms of action, whether by links with aldo-keto reductases (AKR) or by comprising cruzain (CZ) which is one of the key Trypanosoma cruzi development enzymes. The results indicate that for both enzymes, van der Waals interactions between ligand and receptors favor binding and hydrophobic interactions with the phenolic and aliphatic parts of the ligand. The study demonstrates that p-coumarate derivatives are promising molecules for developing new prototypes with antiprotozoal activity.

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“…In normal cells, Rho123 can enter the mitochondrial matrix through the mitochondrial transmembrane potential and the fluorescence intensity decreases or disappears. When it comes to apoptosis and mitochondrial membrane integrity, Rho123 is released outside the mitochondria and expresses a strong green fluorescence ( Hwang et al., 2007 ; de Menezes et al., 2019 ). Cells were treated under the same conditions as described above and were then pre-incubated with 10 μM Rho123 for 30 min at 37°C.…”

Section: Methodsmentioning

confidence: 99%

1α,25(OH)2D3 Radiosensitizes Cancer Cells by Activating the NADPH/ROS Pathway

Nie

et al. 2020

Front. Pharmacol.

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The radioresistance of tumors affect the outcome of radiotherapy. Accumulating data suggest that 1a,25(OH) 2 D 3 is a potential anti-oncogenic molecule in various cancers. In the present study, we investigated the radiosensitive effects and underlying mechanisms of 1a,25(OH) 2 D 3 in vitro and in vivo. We found that 1a,25(OH) 2 D 3 enhanced the radiosensitivity of lung cancer and ovarian cancer cells by promoting the NADPH oxidase-ROS-apoptosis axis. Compared to the group that only received radiation, the survival fraction and selfrenewal capacity of cancer cells treated with a combination of 1a,25(OH) 2 D 3 and radiation were decreased. Both apoptosis and ROS were significantly increased in the combination group compared with the radiation only group. Moreover, N-acetyl-L-cysteine, a scavenger of intracellular ROS, reversed the apoptosis and ROS induced by 1a,25(OH) 2 D 3 , indicating that 1a,25(OH) 2 D 3 enhanced the radiosensitivity of cancer cells in vitro by promoting ROSinduced apoptosis. Moreover, our results demonstrated that 1a,25(OH) 2 D 3 promoted the ROS level via activating NADPH oxidase complexes, NOX4, p22 phox , and p47 phox. In addition, knockdown of the vitamin D receptor (VDR) abolished the radiosensitization of 1a,25(OH) 2 D 3 , which confirmed that 1a,25(OH) 2 D 3 radiosensitized tumor cells that depend on VDR. Similarly, our study also evidenced that vitamin D 3 enhanced the radiosensitivity of cancer cells in vivo and extended the overall survival of mice with tumors. In summary, these results demonstrate that 1a,25(OH) 2 D 3 enhances the radiosensitivity depending on VDR and activates the NADPH oxidase-ROS-apoptosis axis. Our findings suggest that 1a,25 (OH) 2 D 3 in combination with radiation enhances lung and ovarian cell radiosensitivity, potentially providing a novel combination therapeutic strategy.

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Antiparasitic effect of (−)-α-bisabolol against Trypanosoma cruzi Y strain forms

Cited by 26 publications

References 48 publications

Insights of antiparasitic activity of sodium diethyldithiocarbamate against different strains of Trypanosoma cruzi

Insights of antiparasitic activity of sodium diethyldithiocarbamate against different strains of Trypanosoma cruzi

Trypanocidal Mechanism of Action and in silico Studies of p-Coumaric Acid Derivatives

1α,25(OH)2D3 Radiosensitizes Cancer Cells by Activating the NADPH/ROS Pathway

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