From Bench to Bedside: Natural Products and Analogs for the Treatment of Neglected Tropical Diseases (NTDs)

Oliveira, Simone Kobe de; Chiaradia-Delatorre, Louise Domeneghini; Mascarello, Alessandra; Veleirinho, Beatriz; Ramlov, Fernanda; Kuhnen, Shirley; Yunes, Rosendo A.; Maraschin, Marcelo

doi:10.1016/b978-0-444-63460-3.00002-x

Cited by 4 publications

(2 citation statements)

References 239 publications

(220 reference statements)

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“…Natural products used in treating this type of infection are promising [21,22]. For example, hydroxycinnamic acid presents various pharmacological activities: anti-inflammatory, antimicrobial, antioxidant, antitumor, and antiviral [23,24].…”

Section: Introductionmentioning

confidence: 99%

Trypanocidal Mechanism of Action and in silico Studies of p-Coumaric Acid Derivatives

Lopes

Castillo

Monteiro

et al. 2019

IJMS

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Trypanosoma species are responsible for chronic and systemic infections in millions of people around the world, compromising life quality, and family and government budgets. This group of diseases is classified as neglected and causes thousands of deaths each year. In the present study, the trypanocidal effect of a set of 12 ester derivatives of the p-coumaric acid was tested. Of the test derivatives, pentyl p-coumarate (7) (5.16 ± 1.28 μM; 61.63 ± 28.59 μM) presented the best respective trypanocidal activities against both epimastigote and trypomastigote forms. Flow cytometry analysis revealed an increase in the percentage of 7-AAD labeled cells, an increase in reactive oxygen species, and a loss of mitochondrial membrane potential; indicating cell death by necrosis. This mechanism was confirmed by scanning electron microscopy, noting the loss of cellular integrity. Molecular docking data indicated that of the chemical compounds tested, compound 7 potentially acts through two mechanisms of action, whether by links with aldo-keto reductases (AKR) or by comprising cruzain (CZ) which is one of the key Trypanosoma cruzi development enzymes. The results indicate that for both enzymes, van der Waals interactions between ligand and receptors favor binding and hydrophobic interactions with the phenolic and aliphatic parts of the ligand. The study demonstrates that p-coumarate derivatives are promising molecules for developing new prototypes with antiprotozoal activity.

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Section: Introductionmentioning

confidence: 99%

Trypanocidal Mechanism of Action and in silico Studies of p-Coumaric Acid Derivatives

Lopes

Castillo

Monteiro

et al. 2019

IJMS

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“…Flavonoids are one of the largest and most widely distributed groups of secondary plant metabolites. They are polyphenolic compounds showing a common basic structure consisting of a heterocyclic pyran or pyrone ring flanked by a benzene ring on each side (De Oliveira et al, ). During the past two to three decades, the literature on flavonoids and their applications as potential leads to NTDs in scientific journals have increased.…”

Section: Introductionmentioning

confidence: 99%

Flavonoids as efficient scaffolds: Recent trends for malaria, leishmaniasis, Chagas disease, and dengue

Boniface

Ferreira

2019

Phytotherapy Research

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Endemic in 149 tropical and subtropical countries, neglected tropical diseases (NTDs) affect more than 1 billion people annually with over 500,000 deaths. Among the NTDs, some of the most severe consist of leishmaniasis, Chagas disease, and dengue. The impact of the combined NTDs closely rivals that of malaria. According to the World Health Organization, 216 million cases of malaria were reported in 2016 with 445,000 deaths. Current treatment options are associated with various limitations including widespread drug resistance, severe adverse effects, lengthy treatment duration, unfavorable toxicity profiles, and complicated drug administration procedures. Flavonoids are a class of compounds that has been the subject of considerable scientific interest. New developments of flavonoids have made promising advances for the potential treatment of malaria, leishmaniasis, Chagas disease, and dengue, with less toxicity, high efficacy, and improved bioavailability. This review summarizes the current standings of the use of flavonoids to treat malaria and neglected diseases such as leishmaniasis, Chagas disease, and dengue. Natural and synthetic flavonoids are leading compounds that can be used for developing antiprotozoal and antiviral agents. However, detailed studies on toxicity, pharmacokinetics, and mechanisms of action of these compounds are required to confirm the in vitro pharmacological claims of flavonoids for pharmaceutical applications. Highlights In the current review, we have tried to compile recent discoveries on natural and synthetic flavonoids as well as their implication in the treatment of malaria, leishmaniasis, Chagas disease, and dengue. A total of 373 (220 natural and 153 synthetic) flavonoids have been evaluated for antimalarial, antileishmanial, antichagasic, and antidengue activities. Most of these flavonoids showed promising results against the above diseases. Reports on molecular modeling of flavonoid compounds to the disease target indicated encouraging results. Flavonoids can be prospected as potential leads for drug development; however, more rigorously designed studies on toxicity and pharmacokinetics, as well as the quantitative structure–activity relationship studies of these compounds, need to be addressed.

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Road map to the treatment of neglected tropical diseases: Nanocarriers interventions

Joshi

Quadir²,

Yadav³

2021

Journal of Controlled Release

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From Bench to Bedside: Natural Products and Analogs for the Treatment of Neglected Tropical Diseases (NTDs)

Cited by 4 publications

References 239 publications

Trypanocidal Mechanism of Action and in silico Studies of p-Coumaric Acid Derivatives

Trypanocidal Mechanism of Action and in silico Studies of p-Coumaric Acid Derivatives

Flavonoids as efficient scaffolds: Recent trends for malaria, leishmaniasis, Chagas disease, and dengue

Road map to the treatment of neglected tropical diseases: Nanocarriers interventions

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