Discovery of new potent hits against intracellular Trypanosoma cruzi by QSAR-based virtual screening

Melo-Filho, Cleber C.; Braga, Rodolpho C.; Muratov, Eugene; Franco, Caio Haddad; Moraes, Carolina Borsoi; Freitas‐Junior, Lúcio H.; Andrade, Carolina Horta

doi:10.1016/j.ejmech.2018.11.062

Cited by 27 publications

(17 citation statements)

References 34 publications

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“…In addition, many studies utilize computational approaches to identify potential inhibitors of T. cruzi crucial molecular targets (Scarim et al, 2018a,b). Melo-Filho et al, 2019 used a virtual screening based on quantitative structure-activity relationships (QSAR) model to prospect novel molecules against the T. cruzi in commercial database. This model made possible the identification of seven potent and selective compounds against the parasite, which were validated in in vitro experiments.…”

Section: Brief Perspectivementioning

confidence: 99%

Current trends in the pharmacological management of Chagas disease

Ribeiro

Dias

Paiva

et al. 2020

International Journal for Parasitology: Drugs and Drug Resistan

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Chagas disease (CD) is a tropical neglected illness, affecting mainly populations of low socioeconomic status in Latin America. An estimated 6 to 8 million people worldwide are infected with Trypanosoma cruzi, the etiological agent of CD. Despite being one of the main global health problems, this disease continues without effective treatment during the chronic phase of the infection. The limitation of therapeutic strategies has been one of the biggest challenges on the fight against CD. Nifurtimox and benznidazole, developed in the 1970s, are still the only commercial options with established efficacy on CD. However, the efficacy of these drugs have a proven efficacy only during early infection and the benefits in the chronic phase are questionable. Consequently, there is a growing need for new pharmacological alternatives, either by optimization of existing drugs or by the formulation of new compounds. In the present study, a literature review of the currently adopted therapy, its concomitant combination with other drugs, and potential future treatments for CD was performed, considering articles published from 2012. The revised articles were selected according to the protocol of treatment: evaluation of drug association, drug repositioning and research of new drugs. As a result of the present revision, it was possible to conclude that the use of benznidazole in combination with other compounds showed better results when compared with its use as a single therapy. The search of new drugs has been the strategy most used in pursuing more effective forms of treatment for CD. However, studies have still focused on basic research, that is, they are still in a pre-clinical stage, using methodologies based on in vitro or in animal studies.

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Section: Brief Perspectivementioning

confidence: 99%

Current trends in the pharmacological management of Chagas disease

Ribeiro

Dias

Paiva

et al. 2020

International Journal for Parasitology: Drugs and Drug Resistan

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“…Structure-based drug design by virtual screening and molecular docking studies has become a valuable primary step in the identification of novel lead molecules for the treatment of diseases [59,60], and proven to be a very efficient tool for antiviral [61][62][63][64] and antibacterial [65,66] and antiprotozoal [67,68] drug discovery. Therefore, a virtual screening experiment was conducted to determine the interaction of natural ligands of the NPASS database within the binding pocket of putative drug targets of the virus that was calculated in terms of docking scores and MM-GBSA values.…”

Section: Introductionmentioning

confidence: 99%

High throughput virtual screening reveals SARS-CoV-2 multi-target binding natural compounds to lead instant therapy for COVID-19 treatment

Naik

Gupta

Ojha

et al. 2020

International Journal of Biological Macromolecules

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The present-day world is severely suffering from the recently emerged SARS-CoV-2. The lack of prescribed drugs for the deadly virus has stressed the likely need to identify novel inhibitors to alleviate and stop the pandemic. In the present high throughput virtual screening study, we used in silico techniques like receptor-ligand docking, Molecular dynamic (MD), and ADME properties to screen natural compounds. It has been documented that many natural compounds display antiviral activities, including anti-SARS-CoV effect. The present study deals with compounds of Natural Product Activity and Species Source (NPASS) database with known biological activity that probably impedes the activity of six essential enzymes of the virus. Promising drug-like compounds were identified, demonstrating better docking score and binding energy for each druggable targets. After an extensive screening analysis, three novel multi-target natural compounds were predicted to subdue the activity of three/ more major drug targets simultaneously. Concerning the utility of natural compounds in the formulation of many therapies, we propose these compounds as excellent lead candidates for the development of therapeutic drugs against SARS-CoV-2.

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“…In particular, computational techniques directed to studies related to CD can be considered as powerful tools to help in the discovery and the design of selective, potent, and safer drug candidates [ 16 , 17 , 18 , 19 ]. In this study, seven bioactive neolignans ( 1 – 7 ) were isolated from the flower extract of N. leucantha and were, altogether with other related bioactive compounds ( 8 – 50 ), subjected to robust and predictive in silico models, using two-(2D) and three-(3D) dimensional techniques [ 20 , 21 , 22 , 23 , 24 ], as indicated in Figure 1 . It is also worth noting that the use of various techniques to construct predictive models is an important strategy since these approaches employ different and complementary molecular information (for example, bidimensional, steric/electrostatic/hydrophobic features), which helps in the design of new drug candidates.…”

Section: Introductionmentioning

confidence: 99%

Discovery of New Hits as Antitrypanosomal Agents by In Silico and In Vitro Assays Using Neolignan-Inspired Natural Products from Nectandra leucantha

et al. 2021

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In the present study, the phytochemical study of the n-hexane extract from flowers of Nectandra leucantha (Lauraceae) afforded six known neolignans (1–6) as well as one new metabolite (7), which were characterized by analysis of NMR, IR, UV, and ESI-HRMS data. The new compound 7 exhibited potent activity against the clinically relevant intracellular forms of T. cruzi (amastigotes), with an IC50 value of 4.3 μM and no observed mammalian cytotoxicity in fibroblasts (CC50 > 200 μM). Based on the results obtained and our previous antitrypanosomal data of 50 natural and semi-synthetic related neolignans, 2D and 3D molecular modeling techniques were employed to help the design of new neolignan-based compounds with higher activity. The results obtained from the models were important to understand the main structural features related to the biological response of the neolignans and to aid in the design of new neolignan-based compounds with better biological activity. Therefore, the results acquired from phytochemical, biological, and in silico studies showed that the integration of experimental and computational techniques consists of a powerful tool for the discovery of new prototypes for development of new drugs to treat CD.

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Discovery of new potent hits against intracellular Trypanosoma cruzi by QSAR-based virtual screening

Cited by 27 publications

References 34 publications

Current trends in the pharmacological management of Chagas disease

Current trends in the pharmacological management of Chagas disease

High throughput virtual screening reveals SARS-CoV-2 multi-target binding natural compounds to lead instant therapy for COVID-19 treatment

Discovery of New Hits as Antitrypanosomal Agents by In Silico and In Vitro Assays Using Neolignan-Inspired Natural Products from Nectandra leucantha

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