Natural Products: Key Prototypes to Drug Discovery Against Neglected Diseases Caused by Trypanosomatids

Varela, Marina T.; Fernandes, João Paulo S.

doi:10.2174/0929867325666180501102450

Cited by 12 publications

(6 citation statements)

References 47 publications

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“…Both require prolonged treatment, display a wide range of side effects and, although being effective in the acute phase, have a limited efficacy in the chronic stage [32,33]. In this sense, one approach to the development process of new antitrypanosomal drugs has been the search of natural products [34]. In particular, several EOs from plants, such as Alpinia speciosa K. Schum [25], Lippia alba N.E.Br.…”

Section: Discussionmentioning

confidence: 99%

Chemical Composition, Antimicrobial and Antiparasitic Screening of the Essential Oil from Phania matricarioides (Spreng.) Griseb.

Gutiérrez

Scull

Villa³

et al. 2019

Molecules

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Essential oils (EOs) have gained increasing attention due to their pharmacological effectiveness, and they also constitute some of the most popular natural products. In this study, we present the chemical characterization of the EO from Phania matricarioides and the in vitro activity/selectivity against a wide panel of bacteria, fungi and parasitic protozoa. Forty-five compounds were identified in the studied EO, of which lavandulyl acetate (40.1%) and thymyl isobutyrate (13.9%) were the major components. The EO did not inhibit bacterial or fungal growth at the maximum concentration tested (64 µg/mL), although it displayed activity on all evaluated protozoa (IC50 values ranging from 2.2 to 56.6 µg/mL). In parallel, the EO demonstrated a noteworthy cytotoxic activity against peritoneal macrophages (CC50 values of 28.0 µg/mL). The most sensitive microorganism was Trypanosoma cruzi, which had a superior activity (IC50 = 2.2 µg/mL) and selectivity (SI = 13) in respect to other parasitic protozoa and the reference drug (p < 0.05). Further in vivo studies are needed to evaluate the potential use of this EO and the main compounds as antitrypanosomal agents. To our knowledge, this is the first report of chemical characterization and antimicrobial assessment of the EO from P. matricarioides.

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Section: Discussionmentioning

confidence: 99%

Chemical Composition, Antimicrobial and Antiparasitic Screening of the Essential Oil from Phania matricarioides (Spreng.) Griseb.

Gutiérrez

Scull

Villa³

et al. 2019

Molecules

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“…Therefore, alternative chemotherapies must be developed to improve the control and elimination of this group of diseases. Natural products, which have always been an important source of bioactive compounds, are commonly used as the starting material for new drug development [ 14 , 15 , 16 ].…”

Section: Introductionmentioning

confidence: 99%

Identification of Kaurane-Type Diterpenes as Inhibitors of Leishmania Pteridine Reductase I

et al. 2021

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The current treatments against Leishmania parasites present high toxicity and multiple side effects, which makes the control and elimination of leishmaniasis challenging. Natural products constitute an interesting and diverse chemical space for the identification of new antileishmanial drugs. To identify new drug options, an in-house database of 360 kauranes (tetracyclic diterpenes) was generated, and a combined ligand- and structure-based virtual screening (VS) approach was performed to select potential inhibitors of Leishmania major (Lm) pteridine reductase I (PTR1). The best-ranked kauranes were employed to verify the validity of the VS approach through LmPTR1 enzyme inhibition assay. The half-maximal inhibitory concentration (IC50) values of selected bioactive compounds were examined using the random forest (RF) model (i.e., 2β-hydroxy-menth-6-en-5β-yl ent-kaurenoate (135) and 3α-cinnamoyloxy-ent-kaur-16-en-19-oic acid (302)) were below 10 μM. A compound similar to 302, 3α-p-coumaroyloxy-ent-kaur-16-en-19-oic acid (302a), was also synthesized and showed the highest activity against LmPTR1. Finally, molecular docking calculations and molecular dynamics simulations were performed for the VS-selected, most-active kauranes within the active sites of PTR1 hybrid models, generated from three Leishmania species that are known to cause cutaneous leishmaniasis in the new world (i.e., L. braziliensis, L. panamensis, and L. amazonensis) to explore the targeting potential of these kauranes to other species-dependent variants of this enzyme.

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“…In view of looming chemotherapeutic drug resistance, natural products and scaffolds from medicinal plants are being emphasized as leads for drug discovery. Plant-based bioactive compounds have merit over synthetic compounds, considering their unique structural variety, providing an unlimited source of molecules and biological activities [35]. A host of plant extracts or oils and their phytoconstituents (alkaloids, terpenoids, quinones, flavonoids, saponins, phenylpropanoids, flavonoids, lignoids, naphthoquinones, iridoids, and more) have shown promise in vitro and/or in vivo [36][37][38][39][40][41].…”

Section: Natural Products As Source Of Antileishmanial Drugsmentioning

confidence: 99%

Introductory Chapter: Leishmaniasis: An Emerging Clinical Syndrome

Afrin¹,

Hemeg²

2018

Leishmaniases as Re-Emerging Diseases

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Natural Products: Key Prototypes to Drug Discovery Against Neglected Diseases Caused by Trypanosomatids

Abstract: As summary, it can be concluded that natural products are an underestimated source for designing novel agents against these parasites.

Cited by 12 publications

References 47 publications

Chemical Composition, Antimicrobial and Antiparasitic Screening of the Essential Oil from Phania matricarioides (Spreng.) Griseb.

Chemical Composition, Antimicrobial and Antiparasitic Screening of the Essential Oil from Phania matricarioides (Spreng.) Griseb.

Identification of Kaurane-Type Diterpenes as Inhibitors of Leishmania Pteridine Reductase I

Introductory Chapter: Leishmaniasis: An Emerging Clinical Syndrome

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