Brandón Hernández, María del Carmen Cruz, Omar Gómez, Elvia Becerra, Fabiola Eloisa Jiménez, Aarón Mendieta
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引用次数: 0
Abstract
A series of prenylated isoflavones were synthesized to evaluate their inhibitory effect against α-glucosidase and α-amylase enzymes, analyzing the bioisosteric effect of the linear or cyclized prenyl moiety in these benzopyran derivatives. Compound 5a exhibited higher α-glucosidase inhibition (IC50 = 60.5 µM) and lower α-amylase inhibition (IC50 = 85.0 µM) compared to acarbose (IC50 = 527.5 µM for α-glucosidase and 20.1 µM for α-amylase). In contrast, prenylated isoflavone 5c showed higher inhibition in both enzymes (IC50 = 17.6 µM for α-glucosidase and 21.2 µM for α-amylase). This suggests that the attachment of a prenyl moiety to the 7-hydroxy group of isoflavone provides higher inhibition in the enzymes α-glucosidase and α-amylase. Docking studies of compounds 5a and 5c displayed key interactions towards both enzymes. The type of inhibition for 5c was analyzed, where the results indicate a competitive inhibition of both α-glucosidase and α-amylase. Finally, ADMET studies support that compounds 5a and 5c are candidates for the design of novel isoflavones derivatives with antidiabetic potential. Resumen. Una serie de isoflavonas preniladas se sintetizaron para evaluar su efecto inhibidor sobre las enzimas α-glucosidasa y α-amilasa, analizando el efecto bioisotérico del fragmento prenilo tipo lineal o ciclado en estos benzopiranos derivados. El compuesto 5a exhibió una inhibición alta de α-glucosidasa (CI50 = 60.5 µM) y una inhibición más baja de α-amilasa (CI50 = 85.0 µM, respectivamente) en comparación con acarbosa (CI50 = 527.5 y 20.1 µM). La isoflavona prenilada 5c mostró mayor inhibición en ambas enzimas (CI50 = 17.7 µM para α-glucosidasa y 21.2 µM para α-amilasa). Esto sugiere que la unión del fragmento prenilo al hidroxilo de la posición 7 de la isoflavona ocasiona una mayor inhibición en las enzimas α-glucosidasa y α-amilasa. Los compuestos 5a y 5c mostraron interacciones clave hacia el sitio activo de ambas enzimas, de acuerdo con los cálculos de acoplamiento. Se analizó el tipo de inhibición para 5c, donde los resultados indican una inhibición competitiva tanto de α-glucosidasa como de α-amilasa. Finalmente, los estudios ADMET respaldan que los compuestos 5a and 5c son candidatos para el diseño de nuevos derivados de isoflavonas con potencial antidiabético.
期刊介绍:
The Journal of the Mexican Chemical Society (J. Mex. Chem. Soc.) is a scientific, blind, peer reviewed, and open access, free of charge publication that covers all areas of chemistry and its sub-disciplines (i.e. medicinal chemistry, natural products, electrochemistry, material science, computational chemistry, organic chemistry, bionirganic chemistry, etc). It is devoted to facilitating the worldwide advancement of our understanding of chemistry. It will primarily publish original contributions of research in all branches of the theory and practice of chemistry in its broadest context as well as critical reviews in active areas of chemical research where the author has published significant contribution. The J. Mex. Chem. Soc. is a quarterly publication which language of submission and publication is English. To be suitable for publication in J. Mex. Chem. Soc., manuscripts must describe novel aspects of chemistry, high quality of results and discussion an excellent bibliographic support, and contribute to the development of the field. Routine or incremental work are not suitable for publication in J. Mex. Chem. Soc. Authors are encouraged to send contributions in electronic form. Our online submission system guides you stepwise through the process of entering your article details and uploading your files.