In Silico Studies Designed to Select Sesquiterpene Lactones with Potential Antichagasic Activity from an In‐House Asteraceae Database

Herrera‐Acevedo, Chonny; Scotti, Luciana

doi:10.1002/cmdc.201700743

Cited by 41 publications

(35 citation statements)

References 59 publications

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“…An evaluation using structure-based and ligand-based virtual screening was performed to verify potentially active molecules and their possible mechanisms of action, showing potential multitarget molecules. This approach also seeks to minimise the probability of selecting false positive molecules because it considers the scores of virtual tracking techniques and correlates them with the true negative rate [29,30]. The calculation was performed using the following equation: Pc=ps+(1+TN)×p2+TN, IF Pc>0.5 where Pc is the combined probability; ps is the structure-based probability, TN is the true negative rate, and p is the ligand-based probability.…”

Section: Resultsmentioning

confidence: 99%

Larvicidal Compounds Extracted from Helicteres velutina K. Schum (Sterculiaceae) Evaluated against Aedes aegypti L.

et al. 2019

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Helicteres velutina K. Schum (Sterculiaceae), a member of Malvaceae sensu lato, is a Brazilian endemic plant that has been used by the indigenous tribe Pankarare as an insect repellent. A previous study has reported the isolation of terpenoids, flavonoids and pheophytins, in addition to the larvicidal activity of crude H. velutina extracts derived from the aerial components (leaves, branches/twigs, and flowers). The present study reports the biomonitoring of the effects of fractions and isolated compounds derived from H. velutina against A. aegypti fourth instar larvae. A crude ethanol extract was submitted to liquid–liquid extraction with hexane, dichloromethane, ethyl acetate and n-butanol to obtain their respective fractions. Larvicidal evaluations of the fractions were performed, and the hexane and dichloromethane fractions exhibited greater activities than the other fractions, with LC50 (50% lethal concentration) values of 3.88 and 5.80 mg/mL, respectively. The phytochemical study of these fractions resulted in the isolation and identification of 17 compounds. The molecules were subjected to a virtual screening protocol, and five molecules presented potential larvicidal activity after analyses of their applicability domains. When molecular docking was analysed, only three of these compounds showed an ability to bind with sterol carrier protein-2 (1PZ4), a protein found in the larval intestine. The compounds tiliroside and 7,4′-di-O-methyl-8-O-sulphate flavone showed in vitro larvicidal activity, with LC50 values of 0.275 mg/mL after 72 h and 0.182 mg/mL after 24 h of exposure, respectively. This is the first study to demonstrate the larvicidal activity of sulphated flavonoids against A. aegypti. Our results showed that the presence of the OSO3H group attached to C-8 of the flavonoid was crucial to the larvicidal activity. This research supports the traditional use of H. velutina as an alternative insecticide for the control of A. aegypti, which is a vector for severe arboviruses, such as dengue and chikungunya.

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Section: Resultsmentioning

confidence: 99%

Larvicidal Compounds Extracted from Helicteres velutina K. Schum (Sterculiaceae) Evaluated against Aedes aegypti L.

et al. 2019

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“…The biological activity of natural sesquiterpenoids has been extensively investigated, including in trypanosomatids [ 24 , 25 , 26 , 27 ]. Initially, we tested total extracts of three Chilean plants and isolated sesquiterpenoids on infective bloodstream trypomastigotes and proliferative epimastigotes.…”

Section: Discussionmentioning

confidence: 99%

TrypanocidalActivity of Natural Sesquiterpenoids Involves Mitochondrial Dysfunction, ROS Production and Autophagic Phenotype in Trypanosoma cruzi

et al. 2018

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Chagas disease is a neglected tropical disease that is caused by the protozoan Trypanosoma cruzi and represents a serious health problem, especially in Latin America. The clinical treatment of Chagas disease is based on two nitroderivatives that present severe side effects and important limitations. In folk medicine, natural products, including sesquiterpenoids, have been employed for the treatment of different parasitic diseases. In this study, the trypanocidal activity of compounds isolated from the Chilean plants Drimys winteri, Podanthus mitiqui and Maytenus boaria on three T. cruzi evolutive forms (epimastigote, trypomastigote and amastigote) was evaluated. Total extracts and seven isolated sesquiterpenoids were assayed on trypomastigotes and epimastigotes. Polygodial (Pgd) from D. winteri, total extract from P. mitiqui (PmTE) and the germacrane erioflorin (Efr) from P. mitiqui were the most bioactive substances. Pgd, Efr and PmTE also presented strong effects on intracellular amastigotes and low host toxicity. Many ultrastructural effects of these substances, including reservosome disruption, cytosolic vacuolization, autophagic phenotype and mitochondrial swelling (in the case of Pgd), were observed. Flow cytometric analysis demonstrated a reduction in mitochondrial membrane potential in treated epimastigotes and an increase in ROS production and high plasma membrane permeability after treatment with Pgd. The promising trypanocidal activity of these natural sesquiterpenoids may be a good starting point for the development of alternative treatmentsforChagas disease.

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“…An approach combining structure-based and ligand-based virtual screening was realized to verify potentially active molecules as well as their possible mechanism of action, showing potential multitarget molecules. This approach also seeks to minimize the probability of selecting false positive molecules because it considers the scores of both virtual tracking techniques and correlates them with the true negative rate [15,16]. The calculation is done with the following equation:…”

Section: Resultsmentioning

confidence: 99%

Ligand-Based and Structure-Based virtual screening for the discovery of natural inhibitor the Hepatitis C Virus

Barros

Scotti

2018

Proceedings of MOL2NET 2018, International Conference on Multidisciplinary Sciences, 4th Edition

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Hepatitis C is a disease that constitutes a serious global health problem, is often asymptomatic and difficult to diagnose, about 60-80% of infected patients develop chronic diseases over time. As there is no vaccine against hepatitis C virus (HCV), developing new cheap treatments is a big challenge. The search for new drugs from natural products has been outstanding in recent years. The aim of this study was combining structure-based and ligand-based virtual screening (VS) techniques to select potentially active molecules against two HCV target proteins from in-house secondary metabolite dataset (SistematX). From the ChEMBL database, we selected two sets of 1199 and 237 chemical structures with inhibitory activity against different targets of HCV to create random forest models with an accuracy value higher than 72% for cross-validation and test sets. Afterward, a ligand-based virtual screen of the entire 1378 secondary metabolites database stored in SistematX was performed. In addition, a structure-based virtual screening was also performed for the same set of secondary metabolites using molecular docking. Finally, using consensus analyzes approach combining ligand-based and structure-based VS, two alkaloids and one triterpene were selected as potential anti-HCV compounds.

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In Silico Studies Designed to Select Sesquiterpene Lactones with Potential Antichagasic Activity from an In‐House Asteraceae Database

Cited by 41 publications

References 59 publications

Larvicidal Compounds Extracted from Helicteres velutina K. Schum (Sterculiaceae) Evaluated against Aedes aegypti L.

Larvicidal Compounds Extracted from Helicteres velutina K. Schum (Sterculiaceae) Evaluated against Aedes aegypti L.

TrypanocidalActivity of Natural Sesquiterpenoids Involves Mitochondrial Dysfunction, ROS Production and Autophagic Phenotype in Trypanosoma cruzi

Ligand-Based and Structure-Based virtual screening for the discovery of natural inhibitor the Hepatitis C Virus

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