Estudo in silico de compostos fenólicos isolados de Inga laurina

Chagas, Cristian Kallahan Silva; Rolim, Camilla Eduarda Lima; Martins, Hanna Patrícia dos Santos; Dolabela, Maria Fâni

doi:10.33448/rsd-v11i2.25592

Cited by 3 publications

(3 citation statements)

References 30 publications

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“…The remaining compounds violated two criteria established by this rule: log p > 5 and molecular mass>500 Da ( Table 3 ). Although these molecules violated the rule, it does not mean that their therapeutic potential should be ignored ( Lipinski, 2004 ; Chagas and Kallahan, 2022 ).…”

Section: Resultsmentioning

confidence: 99%

“…Despite the high molecular mass of compounds, the results suggest they cross the blood-brain barrier (BBB) freely ( Table 4 ), probably due to their high lipid solubility ( Chagas and Kallahan, 2022 ) ( Table 3 ). It is noteworthy that different types of tumors develop in the central nervous system (CNS) and their growth can be rapid, making it important to develop drugs that can be administered orally and reach therapeutic concentrations in the CNS.…”

Section: Resultsmentioning

confidence: 99%

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In silico studies on cytotoxicity and antitumoral activity of acetogenins from Annona muricata L

Fallon Adido,

Silva Chagas,

Ferreira

et al. 2023

Front. Chem.

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As life expectancy increases, the number of people affected by cancer is increasing. The available drugs still cause several adverse reactions, and it is important to look for less toxic drugs that act on resistant cancers. The present study evaluated the antitumor potential of acetogenins. Through a literature review, 44 acetogenins isolated from Annona muricata were selected and subjected to in silico studies to predict the physicochemical properties, pharmacokinetics (Preadmet and Admet lab), toxicity (Preadmet and Protox II) and molecular docking in caspase 3 (DockThor). For muricatacin, a literature review was carried out for antitumor activity and cytotoxicity. Only muricatacin met all physicochemical criteria, while all compounds showed high cutaneous and intestinal absorption (HIA), moderate permeability in Madin-Darby canine kidney and Caco2 cells, strongly bound plasma proteins, freely crossed the blood-brain barrier, inhibited CYP2C19, CYP2C9 and CYP3A4 and have an affinity for CYP3A4, being metabolized by it, an undesirable characteristic for antitumor drugs. All compounds were toxic in at least one model, while compound 28 was not carcinogenic in rats and mice. Compounds 13, 14, 15, 16, 17 and 28 were selected for molecular docking into Caspase 3. Docking showed hydrophobic interactions, hydrogen and covalent bonds performed to maintain the stability of caspase 3, and cis-uvariamicin IV stood out more through the energies and chemical bonds of this parameter. The chloroform fraction from the methanolic extract of the seeds showed activity against triple-negative breast cancer, both in vitro and in vivo, and only muricatacin has studies in which the antitumor activity was evaluated in vitro and showed to be very promising. In summary, muricatacin and cis-uvariamicin IV appear to be very promising as antitumors, especially cis-uvariamicin IV.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

In silico studies on cytotoxicity and antitumoral activity of acetogenins from Annona muricata L

Fallon Adido,

Silva Chagas,

Ferreira

et al. 2023

Front. Chem.

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“…In this sense, in silico studies allows to evaluate the possibility of a compound having a potential biological effect, as well as to evaluate its pharmacokinetics and toxicity. It is of great relevance to the analysis of isolated secondary metabolites and discards unpromising metabolites (Chagas et al, 2022). The aim of carrying out the present study was to identify the main biological activities, pharmacokinetics, and toxicity, in silico, of the isolated flavonoids present in the cupuaçu seed.…”

Section: Introductionmentioning

confidence: 99%

Biological activity an in silico toxicity of phenolic compounds found in cupuaçu seed (Theobroma grandiflorum)

Ferreira,

Crispim,

Aguiar

et al. 2024

RSD

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Cupuaçu (Theobroma grandiflorum) from the Malvaceae family, has seeds rich in flavonoids. The biological activities of seeds are diverse, however, there are scarce data on these metabolites. The study aimed to evaluate, through in silico methods, the biological, toxicological, and pharmacokinetic potential of metabolites present in the cupuaçu seed. The metabolites hypolaetina 3'-methylether 8-O-β-D glucuronide, theograndin II, hypolaetina 3'-methylether 8-O-β-D 3”-sulfated glucuronide, isoscutellarein 8-0-β-D glucuronide and theograndin I were analysed through Pubchem to search for structures, and PreADMET (pharmacokinetics and toxicity) and PASS online for biological activities (PA >98%). The results demonstrated low human intestinal absorption, in addition to weak to moderate distribution across the blood-brain barrier. All phenolic compounds showed weak to moderate binding to plasma proteins and low permeability in CaCo2 cells, except for isoscutelarein 8-0-β-D glucuronide and hypolaetina 3'-methylether 8-O-β-D glucuronide with moderate permeability, being non-mutagenic. Furthermore, they had the potential to inhibit CYPs, such as CYP-2C9 and CYP-3A4. Also, the structures showed toxicity in Medaka fish, but they did not present toxicity in algae and Daphnia sp. Finally, the molecules presented the following main properties: hemostatic, cardioprotective, and antioxidant action, among others. The compounds presented varied biological activity profiles, but their pharmacokinetic and toxicity were not promising, limiting the potential for developing new drugs. The use of technologies is suggested to transform them into prodrugs, carriers, and the use of molecular modeling.

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In silico studies on leishmanicide activity of limonoids and fatty acids from Carapa guianensis Aubl

de Barros,

Araujo da Costa,

Farias

et al. 2024

Front. Chem.

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The oil of Carapa guianensis showed leishmanicidal activity, with its activity being related to limonoids, but fatty acids are the major constituents of this oil. The present study evaluated the physicochemical, pharmacokinetic, and toxicity profiles of limonoids and fatty acids already identified in the species. Based on these results, 2 limonoids (methyl angosinlate, 6-OH-methyl angosinlate) and 2 fatty acids (arachidic acid; myristic acid) were selected for the prediction of possible targets and molecular docking. Included in this study were: Gedunin, 6α-acetoxygedunin, Methyl angosenlato, 7-deacetoxy-7-oxogedunin, Andirobin, 6-hydroxy-angolensate methyl, 17β-hydroxyazadiradione, 1,2-dihydro-3β-hydroxy-7-deacetoxy-7-oxogedunin, xyllocensin k, 11beta-Hydroxygedunin, 6α,11-11β-diacetoxygedunin, Oleic Acid, Palmitic Acid, Stearic Acid, Arachidic Acid, Myristic Acid, Palmitoleic Acid, Linoleic Acid, Linolenic Acid, and Beenic Acid. Regarding physicochemical aspects, fatty acids violated LogP, and only limonoid 11 violated Lipinski’s rule. A common pharmacokinetic aspect was that all molecules were well absorbed in the intestine and inhibited CYP. All compounds showed toxicity in some model, with fatty acids being mutagenic and carcinogenic, and limonoids not being mutagenic and carcinogenic at least for rats. In in vivo models, fatty acids were less toxic. Molecular dockings were performed on COX-2 steroids (15 and 16) and hypoxia-inducible factor 1 alpha for limonoids (3,6), with this target being essential for the intracellular development of leishmania. Limonoids 3 and 6 appear to be promising as leishmanicidal agents, and fatty acids are promising as wound healers.

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Estudo in silico de compostos fenólicos isolados de Inga laurina

Cited by 3 publications

References 30 publications

In silico studies on cytotoxicity and antitumoral activity of acetogenins from Annona muricata L

In silico studies on cytotoxicity and antitumoral activity of acetogenins from Annona muricata L

Biological activity an in silico toxicity of phenolic compounds found in cupuaçu seed (Theobroma grandiflorum)

In silico studies on leishmanicide activity of limonoids and fatty acids from Carapa guianensis Aubl

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