4′-Hydroxy-6,7-methylenedioxy-3-methoxyflavone: A novel flavonoid from Dulacia egleri with potential inhibitory activity against cathepsins B and L

Novais, Leice M. R. de; Arueira, Cauane C.O. de; Ferreira, Luiz Felipe; Ribeiro, Tereza Auxiliadora Nascimento; Sousa, Paulo Teixeira de; Jacinto, Marcos José; Carvalho, Mário Geraldo de; Júdice, Wagner Alves de Souza; Jesus, Larissa O.P.; Souza, Aline Aparecida de; Torquato, Heron Fernandes Vieira; Paredes‐Gamero, Edgar Julian; Silva, Virginia C.

doi:10.1016/j.fitote.2018.08.005

Cited by 12 publications

(7 citation statements)

References 17 publications

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“…The suggested mechanism of action was the inhibition of pro-cathepsin L-like by the formation of hydrogen bonds between the amino acid TRP 151 of the active site and the carboxyl group of the chalcones [ 46 ]. Isolated flavonoids were also able to inhibit cathepsins L and B in previous studies [ 47 ].…”

Section: Resultsmentioning

confidence: 68%

Flavonoid Derivatives as New Potent Inhibitors of Cysteine Proteases: An Important Step toward the Design of New Compounds for the Treatment of Leishmaniasis

et al. 2023

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Leishmaniasis is a neglected tropical disease, affecting more than 350 million people globally. However, there is currently no vaccine available against human leishmaniasis, and current treatment is hampered by high cost, side-effects, and painful administration routes. It has become a United Nations goal to end leishmaniasis epidemics by 2030, and multitarget drug strategy emerges as a promising alternative. Among the multitarget compounds, flavonoids are a renowned class of natural products, and a structurally diverse library can be prepared through organic synthesis, which can be tested for biological effectiveness. In this study, we synthesised 17 flavonoid analogues using a scalable, easy-to-reproduce, and inexpensive method. All synthesised compounds presented an impressive inhibition capacity against rCPB2.8, rCPB3, and rH84Y enzymes, which are highly expressed in the amastigote stage, the target form of the parasite. Compounds 3c, f12a, and f12b were found to be effective against all isoforms. Furthermore, their intermolecular interactions were also investigated through a molecular modelling study. These compounds were highly potent against the parasite and demonstrated low cytotoxic action against mammalian cells. These results are pioneering, representing an advance in the investigation of the mechanisms behind the antileishmanial action of flavonoid derivatives. Moreover, compounds have been shown to be promising leads for the design of other cysteine protease inhibitors for the treatment of leishmaniasis diseases.

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Section: Resultsmentioning

confidence: 68%

Flavonoid Derivatives as New Potent Inhibitors of Cysteine Proteases: An Important Step toward the Design of New Compounds for the Treatment of Leishmaniasis

et al. 2023

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“…The suggested mechanism of action was inhibition of pro-cathepsin-L-like by the formation of hydrogen bonds between the amino acid TRP 151 of the active site and the carboxyl group of the chalcones [46]. Isolated flavonoids were also able to inhibit cathepsins L and B in previous studies [47].…”

Section: Molecular Modeling Studymentioning

confidence: 85%

“…Factor α =1. 47 shows that molecule 3c has a greater preference to bind to the free enzyme. The factors β = 0.0055 and γ = 0.0115 show that binding of the first molecule to form EI or ESI favored 182 and 87-fold the formation of IEI and IESI, respectively (Table 4).…”

Section: Determination Of Ic50 Mechanism Of Cysteine Protease Inhibit...mentioning

confidence: 98%

Flavonoid Derivatives as New Potent Inhibitors of Cysteine Proteases: An Important Step toward the Design of New Compounds for the Treatment of Leishmaniasis

Lourenço¹,

Iório²,

Silva³

et al. 2022

Preprint

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Leishmaniasis is a neglected tropical disease and affects more than 350 million people worldwide. However, there are no vaccines for humans, and current treatment is hampered due to its high cost, numerous side effects, and painful administration routes. Ending its epidemics by 2030 has become a United Nations goal, and the multitarget drug strategy emerges as a promising alternative. Flavonoids are an example of multitarget compounds and organic synthesis represents a tool to obtain high yields of these molecules. In our study, we synthesized 17 flavonoid analogs using a scalable, easy-to-reproduce, and inexpensive method. All compounds demonstrated an impressive inhibition capacity against rCPB2.8, rCPB3, and rH84Y, which are highly expressed in the amastigote stage, the target form of the parasite. Compounds 3c, f12a, and f12b stood out as effective against all isoforms and intermolecular interactions were investigated through a molecular modeling study. The compounds were highly potent against the parasite and demonstrated low cytotoxic action against mammalian cells. The results were pioneering, representing an advance in the investigation of the mechanisms behind the antileishmanial action of flavonoid derivatives. Furthermore, compounds have shown to be promising leads for the design of other cysteine protease inhibitors for the treatment of leishmaniasis diseases.

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“…With 8 NP classes, the total number of test cases is then 40. The refs − report new NP elucidation of families that we are interested in (see Tables S10–S17). Six different XGBoost models were tested on these cases: five models with the hyperparameters that achieved the highest f1-scores while training with the different resampling techniques and a model that employed a different input representation.…”

Section: Test Casesmentioning

confidence: 99%

Prediction of Natural Product Classes Using Machine Learning and ¹³C NMR Spectroscopic Data

Martínez-Treviño¹,

Uc-Cetina

Fernández-Herrera³

et al. 2020

J. Chem. Inf. Model.

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Structure elucidation of chemical compounds is a complex and challenging activity that requires expertise and well-suited tools. To assign the molecular structure of a given compound, 13C NMR is one of the most widely used techniques because of its broad range of structural information. Taking into account that molecules found in nature can be grouped into natural product (NP) classes because of structural similarities, we explore the possibility of NP class prediction via 13C NMR data. Employing freely available 13C NMR data of NPs, we trained four classifiers for the prediction of eight common NP classes. The best performance was obtained with the XGBoost classifier reaching f1-scores of above 0.82. We also performed experiments with different percentages of positive samples, including the glycoside presence. Furthermore, we tested cases outside the data set, yielding performances above 80% for most classes. For the chromans case, we restricted the test examples to the coumarin subclass, and the prediction accuracy increased to 100%.

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4′-Hydroxy-6,7-methylenedioxy-3-methoxyflavone: A novel flavonoid from Dulacia egleri with potential inhibitory activity against cathepsins B and L

Cited by 12 publications

References 17 publications

Flavonoid Derivatives as New Potent Inhibitors of Cysteine Proteases: An Important Step toward the Design of New Compounds for the Treatment of Leishmaniasis

Flavonoid Derivatives as New Potent Inhibitors of Cysteine Proteases: An Important Step toward the Design of New Compounds for the Treatment of Leishmaniasis

Flavonoid Derivatives as New Potent Inhibitors of Cysteine Proteases: An Important Step toward the Design of New Compounds for the Treatment of Leishmaniasis

Prediction of Natural Product Classes Using Machine Learning and ¹³C NMR Spectroscopic Data

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4′-Hydroxy-6,7-methylenedioxy-3-methoxyflavone: A novel flavonoid from Dulacia egleri with potential inhibitory activity against cathepsins B and L

Cited by 12 publications

References 17 publications

Flavonoid Derivatives as New Potent Inhibitors of Cysteine Proteases: An Important Step toward the Design of New Compounds for the Treatment of Leishmaniasis

Flavonoid Derivatives as New Potent Inhibitors of Cysteine Proteases: An Important Step toward the Design of New Compounds for the Treatment of Leishmaniasis

Flavonoid Derivatives as New Potent Inhibitors of Cysteine Proteases: An Important Step toward the Design of New Compounds for the Treatment of Leishmaniasis

Prediction of Natural Product Classes Using Machine Learning and 13C NMR Spectroscopic Data

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Product

Resources

About

Prediction of Natural Product Classes Using Machine Learning and ¹³C NMR Spectroscopic Data