Plant Terpenoids as Hit Compounds against Trypanosomiasis

Durão, Raquel; Ramalhete, Cátia; Madureira, AM; Mendes, Eduarda; Duarte, Noélia

doi:10.3390/ph15030340

Cited by 5 publications

(2 citation statements)

References 101 publications

(158 reference statements)

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“…More recently, the use of A. paniculata extracts for treatment of mild COVID-19 patients in Thailand has been reported . Additionally, the effect of andrographolide against T. brucei was also reported in the literature, , but its potency against T. cruzi was not previously evaluated. To prove the biological effects of andrographolide, it was isolated from Cymbopogon schoenanthus leaves and tested against amastigote forms of T. cruzi .…”

Section: Introductionmentioning

confidence: 99%

Andrographolide: A Diterpenoid from Cymbopogon schoenanthus Identified as a New Hit Compound against Trypanosoma cruzi Using Machine Learning and Experimental Approaches

Barbosa,

Espinoza,

Amaral

et al. 2023

J. Chem. Inf. Model.

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American Trypanosomiasis, also known as Chagas disease, is caused by the protozoan Trypanosoma cruzi and exhibits limited options for treatment. Natural products offer various structurally complex metabolites with biological activities, including those with anti-T. cruzi potential. The discovery and development of prototypes based on natural products frequently display multiple phases that could be facilitated by machine learning techniques to provide a fast and efficient method for selecting new hit candidates. Using Random Forest and k-Nearest Neighbors, two models were constructed to predict the biological activity of natural products from plants against intracellular amastigotes of T. cruzi. The diterpenoid andrographolide was identified from a virtual screening as a promising hit compound. Hereafter, it was isolated from Cymbopogon schoenanthus and chemically characterized by spectral data analysis. Andrographolide was evaluated against trypomastigote and amastigote forms of T. cruzi, showing IC 50 values of 29.4 and 2.9 μM, respectively, while the standard drug benznidazole displayed IC 50 values of 17.7 and 5.0 μM, respectively. Additionally, the isolated compound exhibited a reduced cytotoxicity (CC 50 = 92.8 μM) against mammalian cells and afforded a selectivity index (SI) of 32, similar to that of benznidazole (SI = 39). From the in silico analyses, we can conclude that andrographolide fulfills many requirements implemented by DNDi to be a hit compound. Therefore, this work successfully obtained machine learning models capable of predicting the activity of compounds against intracellular forms of T. cruzi.

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Section: Introductionmentioning

confidence: 99%

Andrographolide: A Diterpenoid from Cymbopogon schoenanthus Identified as a New Hit Compound against Trypanosoma cruzi Using Machine Learning and Experimental Approaches

Barbosa,

Espinoza,

Amaral

et al. 2023

J. Chem. Inf. Model.

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“…Therefore, the discovery and development of new drugs are urgent, and natural products from plants are a promising approach to achieve this goal. In their comprehensive review, Durão et al [ 17 ] gathered and discussed data published in the literature regarding terpenic compounds with antitrypanosomal activity against T. brucei and T. cruzi , covering the period from 2016 to 2021, and emphasizing the most promising bioactive terpenoids.…”

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confidence: 99%