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In silico screening of anthraquinones from Prismatomeris memecyloides as novel phosphodiesterase type-5 inhibitors (PDE-5Is) / Cribado virtual de antraquinonas procedentes de Prismatomeris memecyloides como inhibidores noveles de fosfodiesterasa tipo 5 (PDE-5Is)
Khanh, Pham Ngoc; Huong, Tran Thu; Spiga, Ottavia; Trezza, Alfonso; Son, Ninh The; Cuong, To Dao; Ha, Vu Thi; Cuong, Nguyen Manh.
Afiliação
  • Khanh, Pham Ngoc; Vietnam Academy of Science and Technology (VAST). Institute of Natural Products Chemistry. Department of Bioactive Products. Hanoi. Viet Nam
  • Huong, Tran Thu; Vietnam Academy of Science and Technology (VAST). Institute of Natural Products Chemistry. Department of Bioactive Products. Hanoi. Viet Nam
  • Spiga, Ottavia; University of Siena. Department of Biotechnology, Chemistry and Pharmacology. Italy
  • Trezza, Alfonso; University of Siena. Department of Biotechnology, Chemistry and Pharmacology. Italy
  • Son, Ninh The; Vietnam Academy of Science and Technology (VAST). Institute of Natural Products Chemistry. Department of Bioactive Products. Hanoi. Viet Nam
  • Cuong, To Dao; Vietnam Academy of Science and Technology (VAST). Institute of Natural Products Chemistry. Department of Bioactive Products. Hanoi. Viet Nam
  • Ha, Vu Thi; Vietnam Academy of Science and Technology (VAST). Institute of Natural Products Chemistry. Department of Bioactive Products. Hanoi. Viet Nam
  • Cuong, Nguyen Manh; Vietnam Academy of Science and Technology (VAST). Institute of Natural Products Chemistry. Department of Bioactive Products. Hanoi. Viet Nam
Rev. int. androl. (Internet) ; 16(4): 147-158, oct.-dic. 2018. ilus, tab, graf
Artigo em Inglês | IBECS | ID: ibc-178043
Biblioteca responsável: ES1.1
Localização: BNCS
ABSTRACT

Objective:

Prismatomeris memecyloides Craib (Rubiaceae) is a medicinal plant traditionally used by ethnic minorities in Vietnam for the treatment of erectile dysfunction (ED). The aim of this study was to investigate the chemical compositions and screen in silico its possible inhibitory effect against PDE-5 which reduced cyclic guanosine-3′,5′-monophosphate (cGMP) levels and indirectly caused the male ED.

Methods:

Separation of natural compounds were carried out on chromatographic column with silica gel or reversed phase materials, eluting with different solvent gradients. The structures of all isolated compounds were elucidated on the basis of spectroscopic data (HR-MS, 1D/2D-NMR). Docking simulation study of compound (1-7) was performed by using flexible side chains protocol based on Iterated Local Search Global Optimizer Algorithm of AutoDock/Vina v.1.1.2. Pharmacokinetic parameters and toxicity prediction were also calculated by appropriate softwares.

Results:

From the methanol extract of roots of P. memecyloides collected in Vietnam, seven compounds including four anthraquinone/one anthraquinone glycoside namely damnacanthal (1), lucidin-ω-methyl ether (2), 3-methylalizarin (3), rubiadin-3-methyl ether (4), and 1-O-methylrubiadin 3-O-primeveroside (5) along with two iridoid glucosides, asperulosidic acid (6) and aitchisonide A (7) were isolated. The molecular modeling results showed that 5 anthraquinone compounds possess the lowest binding energies to PDE-5. The anthraquinone glucoside 1-O-methylrubiadin 3-O-primeveroside (5) potentially inhibited PDE-5 similarly to commercial PDE-5Is sildenafil (SLD) and tadalafil (TLD). Calculated pharmacokinetic results like pIC50,pred; miLogP, TPSA, enzyme inhibitory of anthraquinone glucoside (5) were similar and even higher to those of the commercial PDE-5 inhibitors. Especially the predictive toxicity of 1-O-methylrubiadin 3-O-primeveroside (5) was even lower than those of SLD and TLD.

Conclusion:

This is the first study to find a scientific-based evidence for the ethnic use of P. memecyloides as medicinal plant for the treatment of ED. The result indicates that the anthraquinones (damnacanthal (1), lucidin-ω-methyl ether (2), 3-methylalizarin (3) and rubiadin-3-methyl ether (4)), especially anthraquinone glycoside (1-O-methylrubiadin 3-O-primeveroside (5)) are compounds of potential novel drug class for the ED treatment
RESUMEN

Objetivo:

Prismatomeris memecyloides Craib (Rubiaceae) es una planta medicinal utilizada tradicionalmente por las minorías étnicas en Vietnam para el tratamiento de la disfunción eréctil (DE). El objetivo de este estudio fue investigar sus composiciones químicas y realizar un cribado virtual de su posible efecto inhibitorio frente a PDE-5 con niveles reducidos de guanosín-3′,5′-monofosfato cíclico (cGMP) y la causa indirecta de la DE en los varones.

Métodos:

Se realizó la separación de los componentes naturales en una columna cromatográfica con gel de silicio o materiales de cambio de fase, diluyéndolos con diferentes gradientes de disolventes. Se dilucidaron las estructuras de los componentes aislados sobre la base de los datos espectroscópicos (HR-MS, 1D/2D-NMR). Se realizó el estudio de simulación de acoplamiento del componente (1-7) utilizando el protocolo de cadenas laterales flexibles basado en el algoritmo «Iterated Local Search Global Optimizer» de los parámetros farmacocinéticos AutoDock Vina v.1.1.2., calculándose asímismo la predicción de toxicidad mediante los softwares adecuados.

Resultados:

A partir de los extractos de metanol de las raíces de P. memecyloides recolectadas en Vietnam se aislaron 7 componentes, incluyendo 4 antraquinonas/un glucósido antraquinona denominado damnacantal (1), lucidín-ω-metil éter (2), 3-metilalizarín (3), rubiadín-3-metil éter (4) y 1-O-metilrubiadín 3-O-primeverosida (5) junto con 2 glucósidos iridoides, ácido asperulosídico (6) andaitquisonida A (7). Los resultados de modelación molecular reflejaron que 5 componentes de antraquinona poseen las menores energías de ligamiento a PDE-5. El glucósido antraquinona 1-O-metilrubiadín 3-O-primeverosida (5) inhibió potencialmente PDE-5 de manera similar a las PDE-5Is comerciales sildenafil (SLD) y tadalafil (TLD). Los resultados farmacocinéticos calculados como pIC50, pred, miLogP, TPSA, enzima inhibidora de antraquinona glucósido, 1-O-metilrubiadín 3-O-primoverosida (5), fueron similares e incluso más altos que los de los inhibidores comerciales de PDE-5. Especialmente, la toxicidad predictiva de (5) fue incluso menor que la de SLD y TLD.

Conclusión:

Este es el primer estudio que encuentra una evidencia con base científica para el uso étnico de Prismatormeris memecyloides como planta medicinal para el tratamiento de la DE. El resultado indica que las antraquinonas (damnacantal (1), lucidín-ω-metil éter (2), 3-metilalizarín (3) y rubiadín-3-metil éter (4)), y en especial el glucósido antraquinona (1-O-metilrubiadín 3-O-primeverosida (5)) son componentes de clase farmacológica novel potencial para el tratamiento de la DE
Assuntos
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Coleções: Bases de dados nacionais / Espanha Base de dados: IBECS Assunto principal: Antraquinonas / Inibidores da Fosfodiesterase 5 / Disfunção Erétil Limite: Humanos / Masculino Idioma: Inglês Revista: Rev. int. androl. (Internet) Ano de publicação: 2018 Tipo de documento: Artigo Instituição/País de afiliação: University of Siena/Italy / Vietnam Academy of Science and Technology (VAST)/Viet Nam
Buscar no Google
Coleções: Bases de dados nacionais / Espanha Base de dados: IBECS Assunto principal: Antraquinonas / Inibidores da Fosfodiesterase 5 / Disfunção Erétil Limite: Humanos / Masculino Idioma: Inglês Revista: Rev. int. androl. (Internet) Ano de publicação: 2018 Tipo de documento: Artigo Instituição/País de afiliação: University of Siena/Italy / Vietnam Academy of Science and Technology (VAST)/Viet Nam
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