Synthesis and molecular docking studies of imines as α-glucosidase and α-amylase inhibitors

Aispuro-Pérez, Analy; López-Ávalos, Juan; García-Páez, Fernando; Montes‐Ávila, Julio; Picos-Corrales, Lorenzo A.; Ochoa-Terán, Adrían; Bastidas, Pedro de Jesús Bastidas; Montaño, Sarita; Calderón-Zamora, Loranda; Osuna-Martínez, Ulises; Sarmiento-Sánchez, Juan I.

doi:10.1016/j.bioorg.2019.103491

Cited by 49 publications

(16 citation statements)

References 49 publications

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“…ARG 600 is essential for α‐glucosidase activity (Ur Rehman et al., 2019). The binding energy of the peptides with α‐glucosidase (Table 5) was lower than that reported between acarbose and α‐glucosidase (−4.42 kcal/mol) (Aispuro‐Pérez et al., 2019).…”

Section: Resultsmentioning

confidence: 58%

Characterization of peptides with antioxidant activity and antidiabetic potential obtained from chickpea (Cicer arietinum L.) protein hydrolyzates

Quintero‐Soto

Chávez-Ontiveros

Garzón‐Tiznado

et al. 2021

Journal of Food Science

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Alcalase hydrolyzates were prepared from the albumin (AH) and globulin (GH) fractions of eight chickpea (Cicer arietinum L.) genotypes from Mexico and 10 from other countries. Protein content, antioxidant activity (AA) (ABTS, DPPH), and degree of hydrolysis were evaluated and the best genotype was selected by principal component analysis. The hydrolyzates of the chosen genotype were analyzed for its antidiabetic potential measured as inhibition of α‐amylase, α‐glucosidase, and dipeptidyl peptidase‐4 (DPP4). Peptide profiles were obtained by liquid chromatography‐mass spectrometry (UPLC‐DAD‐MS), and the most active peptides were analyzed by molecular docking. The average antioxidant activity of albumin hydrolyzates was higher than that of globulin hydrolyzates. ICC3761 was the selected genotype and peptides purified from the albumin hydrolyzate showed the best antioxidant activity and antidiabetic potential (FEI, FEL, FIE, FKN, FGKG, and MEE). FEI, FEL, and FIE were in the same chromatographic peak and this mixture showed the best ABTS scavenging (78.25%) and DPP4 inhibition (IC50 = 4.20 µg/ml). MEE showed the best DPPH scavenging (47%). FGKG showed the best inhibition of α‐amylase (54%) and α‐glucosidase (56%) and may be a competitive inhibitor based on in silico‐predicted interactions with catalytic amino acids in the active site of both enzymes. These peptides could be used as nutraceutical supplements against diseases related to oxidative stress and diabetes. Practical Application This study showed that chickpea protein hydrolyzates are good sources of peptides with antidiabetic potential, showing high antioxidant activity and inhibition of enzymes related to carbohydrate metabolism and type 2 diabetes. These hydrolyzates could be formulated in functional foods for diabetes.

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Section: Resultsmentioning

confidence: 58%

Characterization of peptides with antioxidant activity and antidiabetic potential obtained from chickpea (Cicer arietinum L.) protein hydrolyzates

Quintero‐Soto

Chávez-Ontiveros

Garzón‐Tiznado

et al. 2021

Journal of Food Science

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“…[33] Silicon method Molecular docking is a method used to predict the binding site and affinity of small ligand molecules at receptor macromolecular binding sites . [34][35][36][37] The docking process mainly involves spatial and energy matching between the ligand and the receptor to obtain the best conformation, and focuses on their compatibility. Molecular docking can also be used in the screening of αamylase inhibitors to determine whether the small inhibitors have an effect on amylase.…”

Section: Quick Determination Methodsmentioning

confidence: 99%

Proteinaceous α-amylase inhibitors: purification, detection methods, types and mechanisms

Zhou

Zhang

et al. 2021

International Journal of Food Properties

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α-Amylase is abundant in plants and animals. α-Amylase inhibitors can reduce endogenous α-amylase activity, playing an essential role in agricultural pest control, and preventing and treating human disease. In the agricultural field, α-Amylase inhibitors can restrict pest that relies on the starch of crops. Acarbose is an α-amylase inhibitor used to treat diabetes. Some αamylase inhibitors are represented by antinutritional factors, while others are proteinaceous. Depending on their structures and sources, researchers have divided them into seven types: The knottin-like type, the γ-thionin-like type, the cereal type, the Kunitz type, the thaumatin-like type, and the lectin-like type. This paper introduces the methods for separating, purifying, and detecting proteinaceous α-amylase inhibitors while examining the structure and inhibition mechanism of several proteinaceous α-amylase inhibitors. Finally, it explores the potential applications of α-amylase inhibitors.

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“…Furthermore, the derivative 12i was witnessed as the most potent inhibitor of α-glucosidase enzymes as described above; herein, this derivative also proved the most effective inhibitor of α-amylase enzyme, having the lowest IC 50 value (7.52 µM) of all other derivatives and about 2.5-fold smaller than the standard drug, acarbose. This derivative 12i was also found to be a better α-amylase inhibitor as compared to the previously reported nicotinic acid derivatives [75], aryl imines [76], phosphoramidates [77] and piperazine sulfonamide analogs [45]. Moreover, the derivatives 12e and 12f also demonstrated good inhibitory potential against α-amylase, having IC 50 values of 37.5 and 28.97 µM, respectively.…”

Section: α-Amylase Inhibitionmentioning

confidence: 58%

Identification of Cyclic Sulfonamides with an N-Arylacetamide Group as α-Glucosidase and α-Amylase Inhibitors: Biological Evaluation and Molecular Modeling

et al. 2022

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Diabetes mellitus (DM), a complicated metabolic disorder, is due to insensitivity to insulin function or reduction in insulin secretion, which results in postprandial hyperglycemia. α-Glucosidase inhibitors (AGIs) and α-amylase inhibitors (AAIs) block the function of digestive enzymes, which delays the carbohydrate hydrolysis process and ultimately helps to control the postprandial hyperglycemia. Diversified 2-(3-(3-methoxybenzoyl)-4-hydroxy-1,1-dioxido-2H-benzo[e][1,2]thiazin-2-yl)-N-arylacetamides were synthesized and evaluated for their in vitro inhibitory potential against α-glucosidase and α-amylase enzymes. The compounds with chloro, bromo and methyl substituents demonstrated good inhibition of α-glucosidase enzymes having IC50 values in the range of 25.88–46.25 μM, which are less than the standard drug, acarbose (IC50 = 58.8 μM). Similarly, some derivatives having chloro, bromo and nitro substituents were observed potent inhibitors of α-amylase enzyme, with IC50 values of 7.52 to 15.06 μM, lower than acarbose (IC50 = 17.0 μM). In addition, the most potent compound, N-(4-bromophenyl)-2-(4-hydroxy-3-(3-methoxybenzoyl)-1,1-dioxido-2H-benzo[e][1,2]thiazin-2-yl)acetamide (12i), was found to be a non-competitive and competitive inhibitor of α-glucosidase and α-amylase enzymes, respectively, during kinetic studies. The molecular docking studies provided the binding modes of active compounds and the molecular dynamics simulation studies of compound 12i in complex with α-amylase also showed that the compound is binding in a fashion similar to that predicted by molecular docking studies.

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Synthesis and molecular docking studies of imines as α-glucosidase and α-amylase inhibitors

Cited by 49 publications

References 49 publications

Characterization of peptides with antioxidant activity and antidiabetic potential obtained from chickpea (Cicer arietinum L.) protein hydrolyzates

Characterization of peptides with antioxidant activity and antidiabetic potential obtained from chickpea (Cicer arietinum L.) protein hydrolyzates

Proteinaceous α-amylase inhibitors: purification, detection methods, types and mechanisms

Identification of Cyclic Sulfonamides with an N-Arylacetamide Group as α-Glucosidase and α-Amylase Inhibitors: Biological Evaluation and Molecular Modeling

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