Alpha-glucosidase and Alpha-amylase Inhibitors Derived from Naturally Occurring Prenylated Isoflavones

IF 1.1 4区 化学 Q3 CHEMISTRY, MULTIDISCIPLINARY Journal of the Mexican Chemical Society Pub Date : 2024-01-01 DOI:10.29356/jmcs.v68i1.2129
Brandón Hernández, María del Carmen Cruz, Omar Gómez, Elvia Becerra, Fabiola Eloisa Jiménez, Aarón Mendieta
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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.
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从天然异黄酮中提取的α-葡萄糖苷酶和α-淀粉酶抑制剂
为了评估其对α-葡萄糖苷酶和α-淀粉酶的抑制作用,我们合成了一系列前炔基异黄酮,分析了这些苯并吡喃衍生物中线性或环化前炔基的生物异构效应。与阿卡波糖(α-葡萄糖苷酶的 IC50 = 527.5 µM,α-淀粉酶的 IC50 = 20.1 µM)相比,化合物 5a 表现出更高的α-葡萄糖苷酶抑制率(IC50 = 60.5 µM)和更低的α-淀粉酶抑制率(IC50 = 85.0 µM)。相比之下,前炔化异黄酮 5c 对这两种酶的抑制作用更大(α-葡萄糖苷酶的 IC50 = 17.6 µM,α-淀粉酶的 IC50 = 21.2 µM)。这表明,在异黄酮的 7-羟基上附着一个芳基,可对α-葡萄糖苷酶和α-淀粉酶产生更强的抑制作用。化合物 5a 和 5c 的对接研究显示了对这两种酶的关键相互作用。对 5c 的抑制类型进行了分析,结果表明其对α-葡萄糖苷酶和α-淀粉酶都有竞争性抑制作用。最后,ADMET 研究证明化合物 5a 和 5c 是设计具有抗糖尿病潜力的新型异黄酮衍生物的候选化合物。 概述。通过分析这些苯并吡喃衍生物中线性或环化的前酰基片段的生物异构效应,合成了一系列前酰基异黄酮,以评估它们对α-葡萄糖苷酶和α-淀粉酶的抑制作用。与阿卡波糖(CI50 = 527.5 和 20.1 µM)相比,化合物 5a 表现出较高的α-葡萄糖苷酶抑制率(CI50 = 60.5 µM)和较低的α-淀粉酶抑制率(CI50 = 85.0 µM)。前炔化异黄酮 5c 对这两种酶的抑制率更高(α-葡萄糖苷酶的 CI50 = 17.7 µM,α-淀粉酶的 CI50 = 21.2 µM)。这表明,前酰基片段与异黄酮第 7 位的羟基结合会增加对 α-葡萄糖苷酶和 α-淀粉酶的抑制作用。根据对接计算,化合物 5a 和 5c 对这两种酶的活性位点显示出关键的相互作用。对 5c 的抑制类型进行了分析,结果表明其对α-葡萄糖苷酶和α-淀粉酶都有竞争性抑制作用。最后,ADMET 研究证明化合物 5a 和 5c 是设计具有抗糖尿病潜力的新异黄酮衍生物的候选化合物。
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来源期刊
CiteScore
2.00
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审稿时长
6-12 weeks
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.
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