γ‐Lactones from Persea americana and Persea fulva –in vitro and in silico evaluation of Trypanosoma cruzi activity

2021 ◽  
Author(s):  
Isabella Reis ◽  
Eric Umehara ◽  
Rodrigo Conceição ◽  
Larissa Oliveira ◽  
Manoelito Junior ◽  
...  
Keyword(s):  
Trypanosoma Cruzi ◽  
In Silico ◽  
Persea Americana

scholarly journals Anti-parasitic effect of novel amidines against Trypanosoma cruzi: phenotypic and in silico absorption, distribution, metabolism, excretion and toxicity analysis

2017 ◽  
Vol 3 ◽  
Author(s):  
ALINE SILVA DA GAMA NEFERTITI ◽  
MARCOS MEUSER BATISTA ◽  
PATRÍCIA BERNARDINO DA SILVA ◽  
EDUARDO CAIO TORRES-SANTOS ◽  
EDEZIO F. CUNHA-JÚNIOR ◽  
...  
Keyword(s):  
Trypanosoma Cruzi ◽  
In Silico ◽  
Host Cells ◽  
Mammalian Host ◽  
Aromatic Molecules ◽  
Toxicity Analysis ◽  
Parasitic Effect ◽  
The Many ◽  
Discrete Typing Unit

SUMMARYNew more selective and potent drugs are urgently need to treat Chagas disease (CD). Among the many synthetic compounds evaluated againstTrypanosoma cruzi, aromatic amidines (AAs) and especially arylimidamides (AIAs) have potent activity against this parasite. Presently, the effect of four mono-amidines (DB2228, DB2229, DB2292 and DB2294), four diamidines (DB2232, DB2235, DB2251 and DB2253) and one AIA (DB2255) was screenedin vitroagainst different forms (bloodstream trypomastigotes – BT and intracellular forms) and strains from discrete typing unit (DTU) I and VI ofT. cruziand their cytotoxic profile on mammalian host cells. Except for DB2253, all molecules were as active as benznidazole (Bz), resulting in 50% of reduction in the number of alive BT, with EC50ranging from 2·7 to 10·1µmafter 24 h of incubation. DB2255 was also the most potent against amastigotes (Tulahuen strain) showing similar activity to that of Bz (3µm).In silicoabsorption, distribution, metabolism, excretion and toxicity analysis demonstrated probability of human intestinal adsorption, while mutagenicity and inhibition of hERG1 were not predicted, besides giving acceptable predicted volumes of distribution. Our findings contribute for better knowledge regarding the biological effect of this class of aromatic molecules againstT. cruziaiming to identify novel promising agent for CD therapy.

scholarly journals In Vitro, In Silico, and In Vivo Analyses of Novel Aromatic Amidines against Trypanosoma cruzi

2017 ◽  
Vol 62 (2) ◽  
Author(s):  
Camila C. Santos ◽  
Jéssica R. Lionel ◽  
Raiza B. Peres ◽  
Marcos M. Batista ◽  
Patrícia B. da Silva ◽  
...  
Keyword(s):  
Body Weight ◽  
Trypanosoma Cruzi ◽  
In Silico ◽  
Selective Agent ◽  
Content Type ◽  
Main Target ◽  
Target Fishing ◽  
Assay Interference

ABSTRACT Five bis-arylimidamides were assayed as anti-Trypanosoma cruzi agents by in vitro, in silico, and in vivo approaches. None were considered to be pan-assay interference compounds. They had a favorable pharmacokinetic landscape and were active against trypomastigotes and intracellular forms, and in combination with benznidazole, they gave no interaction. The most selective agent (28SMB032) tested in vivo led to a 40% reduction in parasitemia (0.1 mg/kg of body weight/5 days intraperitoneally) but without mortality protection. In silico target fishing suggested DNA as the main target, but ultrastructural data did not match.

Activity of a hydroxybibenzyl bryophyte constituent against Leishmania spp. and Trypanosoma cruzi: In silico, in vitro and in vivo activity studies

2008 ◽  
Vol 43 (9) ◽  
pp. 1797-1807 ◽  
Author(s):  
Virginia Roldos ◽  
Hector Nakayama ◽  
Miriam Rolón ◽  
Alina Montero-Torres ◽  
Fernando Trucco ◽  
...  
Keyword(s):  
Trypanosoma Cruzi ◽  
In Silico ◽  
Leishmania Spp

scholarly journals Efficacy of sertraline against Trypanosoma cruzi: an in vitro and in silico study

2018 ◽  
Vol 24 (1) ◽  
Author(s):  
Daiane Dias Ferreira ◽  
Juliana Tonini Mesquita ◽  
Thais Alves da Costa Silva ◽  
Maiara Maria Romanelli ◽  
Denise da Gama Jaen Batista ◽  
...  
Keyword(s):  
Trypanosoma Cruzi ◽  
In Silico ◽  
In Silico Study

Synthesis and biological evaluation in vitro and in silico of N-propionyl-N′-benzeneacylhydrazone derivatives as cruzain inhibitors of Trypanosoma cruzi

2020 ◽  
Author(s):  
Timoteo Delgado-Maldonado ◽  
Benjamín Nogueda-Torres ◽  
José C. Espinoza-Hicks ◽  
Lenci K. Vázquez-Jiménez ◽  
Alma D. Paz-González ◽  
...  
Keyword(s):  
Trypanosoma Cruzi ◽  
In Silico ◽  
Biological Evaluation ◽  
Synthesis And Biological Evaluation ◽  
Cruzain Inhibitors

In vitro and in silico evaluations of new aryloxy-1,4-naphthoquinones as anti-Trypanosoma cruzi agents

2020 ◽  
Vol 29 (4) ◽  
pp. 665-674 ◽  
Author(s):  
Alejandra González ◽  
Nohemí Becerra ◽  
Muhammad Kashif ◽  
Mercedes González ◽  
Hugo Cerecetto ◽  
...  
Keyword(s):  
Trypanosoma Cruzi ◽  
In Silico

scholarly journals In Vitro Phenotypic Activity and In Silico Analysis of Natural Products from Brazilian Biodiversity on Trypanosoma cruzi

Molecules ◽  
2021 ◽  
Vol 26 (18) ◽  
pp. 5676
Author(s):  
Raiza B. Peres ◽  
Ludmila F. de A. Fiuza ◽  
Patrícia B. da Silva ◽  
Marcos M. Batista ◽  
Flávia da C. Camillo ◽  
...  
Keyword(s):  
Natural Products ◽  
Trypanosoma Cruzi ◽  
In Silico ◽  
In Silico Analysis ◽  
Mammalian Host ◽  
Reference Drug ◽  
Wide Range ◽  
Pure Compounds ◽  
Silico Analysis

Chagas disease (CD) affects more than 6 million people worldwide. The available treatment is far from ideal, creating a demand for new alternative therapies. Botanical diversity provides a wide range of novel potential therapeutic scaffolds. Presently, our aim was to evaluate the mammalian host toxicity and anti-Trypanosoma cruzi activity of botanic natural products including extracts, fractions and purified compounds obtained from Brazilian flora. In this study, 36 samples of extracts and fractions and eight pure compounds obtained from seven plant species were evaluated. The fraction dichloromethane from Aureliana fasciculata var. fasciculata (AFfPD) and the crude extract of Piper tectoniifolium (PTFrE) showed promising trypanosomicidal activity. AFfPD and PTFrE presented EC50 values 10.7 ± 2.8 μg/mL and 12.85 ± 1.52 μg/mL against intracellular forms (Tulahuen strain), respectively. Additionally, both were active upon bloodstream trypomastigotes (Y strain), exhibiting EC50 2.2 ± 1.0 μg/mL and 38.8 ± 2.1 μg/mL for AFfPD and PTFrE, respectively. Importantly, AFfPD is about five-fold more potent than Benznidazole (Bz), the reference drug for CD, also reaching lower EC90 value (7.92 ± 2.2 μg/mL) as compared to Bz (23.3 ± 0.6 μg/mL). Besides, anti-parasitic effect of eight purified botanic substances was also investigated. Aurelianolide A and B (compounds 1 and 2) from A. fasciculata and compound 8 from P. tuberculatum displayed the best trypanosomicidal effect. Compounds 1, 2 and 8 showed EC50 of 4.6 ± 1.3 μM, 1.6 ± 0.4 μM and 8.1 ± 0.9 μM, respectively against intracellular forms. In addition, in silico analysis of these three biomolecules was performed to predict parameters of absorption, distribution, metabolism and excretion. The studied compounds presented similar ADMET profile as Bz, without presenting mutagenicity and hepatotoxicity aspects as predicted for Bz. Our findings indicate that these natural products have promising anti-T. cruzi effect and may represent new scaffolds for future lead optimization.

scholarly journals In Vitro, In Vivo, and In Silico Studies of Cumanin Diacetate as a Potential Drug against Trypanosoma cruzi Infection

ACS Omega ◽  
2021 ◽  
Author(s):  
Andrés Sánchez Alberti ◽  
María F. Beer ◽  
Natacha Cerny ◽  
Augusto E. Bivona ◽  
Lucas Fabian ◽  
...  
Keyword(s):  
Trypanosoma Cruzi ◽  
In Silico ◽  
Potential Drug ◽  
In Silico Studies ◽  
Cruzi Infection
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