Α-amylase Inhibitory Potential Research Articles

Anti-diabetic activity-guided isolation of α-amylase and α-glucosidase inhibitory terpenes from Capsella bursa-pastoris Linn.

Abstract The hypoglycaemic and hypolipidemic potential of ethanol extract of C. bursa-pastoris (ECbp) in streptozotocin (STZ)-provoked diabetic rats was evaluated, and compounds with their α-amylase and α-glucosidase inhibitory potential were isolated. Acute oral toxicity was evaluated in rats. Streptozotocin (STZ) (50 mg/kg body weight) was injected intraperitoneally into rats for diabetes induction. In diabetic rats, ECbp (0.2 g/kg b.w, p.o.) was administered orally for 21 days, and its outcome on blood glucose levels and body weight was observed on a weekly basis besides lipid profile. Compound isolation from ECbp was performed using column chromatography. Oral feeding of ECbp did not produce any toxic effects or death at a dose of 2,000 mg/kg body weight. A serum glucose reduction trend was observed in rats fed with glucose pre-treated with 200 mg/kg b.w. ECbp also appreciably (p < 0.001, p < 0.01, and p < 0.05) diminished raised blood glucose with decreased blood cholesterol levels and led to increased serum high-density lipoprotein levels in comparison to diabetic control rats. Body weight levels were considerably higher (p < 0.05) in diabetic rats treated with ECbp than in diabetic control rats. Isolation of two terpene derivatives (ECbp-1 and ECbp-2) was performed using ECbp, which exhibits significant α-amylase and α-glucosidase inhibition.

Valorization of Wine Lees: Assessment of Antioxidant, Antimicrobial and Enzyme Inhibitory Activity of Wine Lees Extract and Incorporation in Chitosan Films

AbstractWine lees, as one of the main by-products of winery wastes, is considered a rich source of bioactive compounds such as polyphenols. Recovery of such bioactive compounds would amplify the valorization of winery by-products, as well as promote their use in cosmetics and health applications. Towards this aim, the objective of this work is the recovery of phenolic compounds from wine lees by ultrasound-assisted extraction. The effect of extraction time, and ethanol content on the extraction yield of total phenolics was investigated, while the phenolic profile of the extract was monitored by GC-MS. Under the optimized conditions, the total phenolic content was calculated at 302.6 mg gallic acid equivalents g− 1 dry extract; the dry extract was investigated for its biological activities, exhibiting excellent antioxidant and antimicrobial activity. Moreover, the extract was found to be a potent inhibitor of tyrosinase, elastase, collagenase, α-glucosidase, and α-amylase with IC50 values of 53.3, 83.5, 82.7, 19.0, and 31.3 µg mL− 1, respectively. Finally, the wine lees dry extract was incorporated into chitosan films, reinforcing the properties of the films, and providing them with excellent antioxidant activity. The results support that wine lees extract exhibits high antioxidant activity and can be used as a highly efficient inhibitor of enzymes with pharmaceutical and health interest. Moreover, the chitosan film enriched with wine lees extract is a promising material with high antioxidant potential and can lead to the development of novel food packaging films in the food industry. Graphical Abstract

Rhodanine-benzamides as potential hits for α-amylase enzyme inhibitors and radical (DPPH and ABTS) scavengers.

A series of 3-substituted and 3,5-disubstituted rhodanine-based derivatives were synthesized from 3-aminorhodanine and examined for α-amylase inhibitory, DPPH (1,1-diphenyl-2-picrylhydrazyl) and ABTS (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) radical scavenging activities in vitro. These derivatives displayed significant α-amylase inhibitory potential with IC50 values of 11.01-56.04 µM in comparison to standard acarbose (IC50 = 9.08 ± 0.07 µM). Especially, compounds 7 (IC50 = 11.01 ± 0.07 µM) and 8 (IC50 = 12.01 ± 0.07 µM) showed highest α-amylase inhibitory activities among the whole series. In addition to α-amylase inhibitory activity, all compounds also demonstrated significant scavenging activities against DPPH and ABTS radicals, with IC50 values ranging from 12.24 to 57.33 and 13.29-59.09 µM, respectively, as compared to the standard ascorbic acid (IC50 = 15.08 ± 0.03 µM for DPPH; IC50 = 16.09 ± 0.17 µM for ABTS). These findings reveal that the nature and position of the substituents on the phenyl ring(s) are crucial for variation in the activities. The structure-activity relationship (SAR) revealed that the compounds bearing an electron-withdrawing group (EWG) at para substitution possessed the highest activity. In kinetic studies, only the km value was changed, with no observed changes in Vmax, indicating a competitive inhibition. Molecular docking studies revealed important interactions between compounds and the α-amylase active pocket. Further advanced research needs to perform on the identified compounds in order to obtain potential antidiabetic agents.

Exploring the synthesis, molecular structure and biological activities of novel Bis-Schiff base derivatives: A combined theoretical and experimental approach

A library of six novel bis-Schiff base derivatives (2a-f) were synthesized, characterized through modern spectroscopic techniques and screened for their α-glucosidase and α-amylase inhibitory activities (in vitro). In the series, compound 2a (IC50 = 5.64 ± 2.22 µM) and 2f (IC50 = 22.78 ± 2.37 µM) were the most potent α-amylase inhibitors while the remaining four compounds showed significant to less activity. In case of α-glucosidase inhibition, four compounds 2e (IC50 = 2.83 ± 0.18 µM), 2c (IC50 = 7.03 ± 0.15 µM), 2f (IC50 = 9.99 ± 0.20 µM), and 2d (IC50 = 14.68 ± 0.21 µM) displayed excellent inhibitory activity while two compounds showed good inhibitory activity, comparing with the standard acarbose drug. The DFT assay was used to measure the FMO of the synthesized molecules, which indicated their stability, bioactivity and charge transfer. The MEP analysis revealed the distribution of electrostatic potential on the molecular surface of 2a-f, which is helpful for understanding reactivity and interactions. The AIM study showed low hydrogen bond energy and non-covalent interactions. This implies that these molecules may have weak hydrogen bonding and non-covalent interactions, which could affect their chemical behavior. The molecular docking study has provided valuable insights into the interactions between the synthesized derivatives of 2,4-dihydroxyacetophenone with α-glucosidase and α-amylase proteins. The results not only shed light on the binding affinity and key interaction sites but also offer potential avenues for the design of novel drug candidates to control postprandial glucose level in diabetic patients.

Biochemical characterization of bioinspired nanosuspensions from Swertia chirayita extract and their therapeutic effects through nanotechnology approach.

Swertia chirayita is used as a traditional medicinal plant due to its pharmacological activities, including antioxidant, antidiabetic, antimicrobial, and cytotoxic. This study was aimed to evaluate the therapeutic efficacy of newly synthesized nanosuspensions from Swertia chirayita through nanotechnology for enhanced bioactivities. Biochemical characterization was carried out through spectroscopic analyses of HPLC and FTIR. Results revealed that extract contained higher TPCs (569.6 ± 7.8 mg GAE/100 g)) and TFCs (368.5 ± 9.39 mg CE/100 g) than S. chirayita nanosuspension, TPCs (500.6 ± 7.8 500.6 ± 7.8 mg GAE/100 g) and TFCs (229.5± 3.85 mg CE/100 g). Antioxidant activity was evaluated through DPPH scavenging assay, and nanosuspension exhibited a lower DPPH free radical scavenging potential (06 ±3.61) than extract (28.9± 3.85). Anti-dabetic potential was assessed throughα-amylase inhibition and anti-glycation assays. Extract showed higher (41.4%) antiglycation potential than 35.85% nanosuspension and 19.5% α-amylase inhibitory potential than 5% nanosuspension. Biofilm inhibition activity against E. coli was higher in nanosuspension (69.12%) than extract (62.08%). The extract showed high cytotoxicity potential (51.86%) than nanosuspension (33.63%). These nanosuspensions possessed enhanced bioactivities for therapeutic applications could be explored further for the development of new drugs.

Synthesis of Some Novel 4-bromobenzoic Acid Clubbed Hydrazone Schiff Base Derivatives as Potent α-amylase Inhibitors: In vitro and In silico Studies

Aims:: Synthesis of novel 4-bromobenzoic acid-based hydrazone-Schiff base derivatives and to screen them for their α-amylase inhibitory activity. Objective:: The biological activities of hydrazone-Schiff base compounds encouraged us to evaluate the synthesized derivatives (4-32) for in-vitro inhibition activity against the α-amylase enzyme. Methods:: In current research work twenty-nine Schiff base derivatives (4-32) of 4-bromobenzoic acid were synthesized in worthy yields by treating various replaced aldehydes with 4- bromobenzohydrazide using methanol solvent in catalytic quantity of acetic acid. The products were structurally described through the support of several spectroscopic methods (EI-MS and 1HNMR) and finally evaluated against α-amylase enzyme. Results:: All the made derivatives exhibited worthy inhibition potential from IC50 = 0.21 ± 0.01 to 5.50 ± 0.01 μM when equated to the usual acarbose drug having IC50 = 1.34 ± 0.01 μM. Compound 21 (IC50 = 0.21 ± 0.01 μM) was established as the most active inhibitor among the series better than standard. The structure-activity relationship study showed that the alteration in the activity of the produced products might be due to the attached position and nature of the substituents. Furthermore, in-silico study supported the effects of groups attached on the binding interaction with α-amylase enzyme. Conclusion:: A series of substituted hydrazone Schiff bases based on 4-bromobenzoic acid were produced, confirmed the structures by EI-MS and 1H-NMR spectroscopic methods and lastly tested for their in-vitro α-amylase inhibitory potential. Among the series, twenty-four products indicated brilliant inhibition potential having IC50 values from 0.21 ± 0.01 to 1.30 ± 0.01 μM. The structure-activity relationship study showed that the alteration in the activity of the synthesized products might be due to the attached position and nature of the substituents. On the other hand, in silico studies advocated that the synthesized Schiff base derivatives have prevalent interactions of binding within the active site of the α-amylase enzyme, and because of their various attached substituent, their conformation is altered in the active site of the enzyme. The current study recognized a number of lead candidates derived from 4-bromobenzoic acid. Additional investigation of the synthesized derivatives for coming research to get novel α-amylase inhibitors.

Efficiency of some inhibitors on alpha amylase of the peach fruit fly larvae Bactrocera zonata (Saunders) (Diptera: Tephritidae)

Alpha amylase inhibitor (α-AI) extracted from wheat grains (Triticum sp.) as possible new agent in pest control, and some other organic inhibitors are evaluated against α-amylase of the fourth larval instar of the peach fruit fly (PFF) larvae; Bactrocera zonata (Saund.). 4.2 mg protein ml−1 of the inhibitor extracted by 70 % ammonium sulphate inhibited, in vitro, 97.9 % of amylolytic activity of the larvae. Percent inhibition efficiency (Ei%) of the crude inhibitor was directly proportional with its concentration in the range from 4.2 to 0.21 mg protein ml-1. The calculated IC50 was 1 mg protein ml-1. Increasing of the surrounding temperature from 10 to 35 °C not enhanced inhibitor efficiency, and the inhibitor could inhibit the enzyme efficiently at a relatively low temperature (10 °C). On the other hand, wheat extract showed quick binding affinity to α-amylase of PFF larvae. Incubation of the inhibitor with the enzyme for 10 min was sufficient for wheat α- AI to exert its maximum inhibition. Screening of other possible organic compounds act as α-AI such as citric, gallic and acetic acids showed that gallic acid was the most potent inhibitor, and it was able to inhibit α-amylase of the larvae, at a relatively, low concentration (10−4M). It could be concluded that there are natural potent inhibitors of PFF α-amylase which act as a key enzyme for carbohydrates digestion. This might be useful as an alternative method for controlling B. zonata population. Additional experiments are necessary to make these alternative compounds applicable in the field.

The substitution sites of hydroxyl and galloyl groups determine the inhibitory activity of human pancreatic α-amylase in twelve tea polyphenol monomers

Tea polyphenols have been reported as potential α-amylase inhibitors. However, the quantitative structure–activity relationship (QSAR) between tea polyphenols and human pancreas α-amylase (HPA) is not well understood. Herein, the inhibitory effect of twelve tea polyphenol monomers on HPA was investigated in terms of inhibitory activity, as well as QSAR analysis and interaction mechanism. The results revealed that the HPA inhibitory activity of theaflavins (TFs), especially theaflavin-3′-gallate (TF-3′-G, IC50: 0.313 mg/mL), was much stronger than that of catechins (IC50: 18.387–458.932 mg/mL). The QSAR analysis demonstrated that the determinant for the inhibitory activity of HPA was not the number of hydroxyl and galloyl groups in tea polyphenol monomers, while the substitution sites of these groups potentially might play a more important role in modulating the inhibitory activity. The inhibition kinetics and molecular docking revealed that TF-3′-G as a mixed-type inhibitor had the lowest inhibition constant and bound to the active sites of HPA with the lowest binding energy (−7.74 kcal/mol). These findings could provide valuable insights into the structures-activity relationships between tea polyphenols and the HPA inhibitors.

Inhibitory effect of extracts from edible parts of nuts on α-amylase activity: a systematic review.

Elevated blood glucose concentration is a risk factor for developing metabolic dysfunction and insulin resistance, leading to type 2 diabetes and cardiovascular diseases. Nuts have the potential to inhibit α-amylase activity, and so lower postprandial glucose, due to their content of polyphenols and other bioactive compounds. We conducted a systematic literature review to assess the ability of extracts from commonly consumed edible parts of nuts to inhibit α-amylase. Among the 31 included papers, only four utilised human α-amylases. These papers indicated that polyphenol-rich chestnut skin extracts exhibited strong inhibition of both human salivary and pancreatic α-amylases, and that a polyphenol-rich almond skin extract was a potent inhibitor of human salivary α-amylase. The majority of the reviewed studies utilised porcine pancreatic α-amylase, which has ∼86% sequence homology with the corresponding human enzyme but with some key amino acid variations located within the active site. Polyphenol-rich extracts from chestnut, almond, kola nut, pecan and walnut, and peptides isolated from cashew, inhibited porcine pancreatic α-amylase. Some studies used α-amylases sourced from fungi or bacteria, outcomes from which are entirely irrelevant to human health, as they have no sequence homology with the human enzyme. Given the limited research involving human α-amylases, and the differences in inhibition compared to porcine enzymes and especially enzymes from microorganisms, it is recommended that future in vitro experiments place greater emphasis on utilising enzymes sourced from humans to facilitate a reliable prediction of effects in intervention studies.

Semi-synthesis, α-amylase inhibition, and kinetic and molecular docking studies of arylidene-based sesquiterpene coumarins isolated from Ferula tunetana Pomel ex Batt.

Despite all the significant progresses made to enhance the efficacy of the existing bank of drugs used to manage and cure type II diabetes mellitus, there is still a need to search and develop novel bioactive compounds with superior efficacy and minimal adverse effects. This study describes the valorization of the natural bioactive sesquiterpene coumarin via the semi-synthesis of new analogs and the study of their α-amylase inhibition activity. The sesquiterpene coumarin named coladonin (1) was quantitatively isolated from the chloroform extract of endemic Ferula tunetana roots. Subsequently, the oxidation of 1via the Jones oxidation reaction, used as a key reaction, afforded precursor 2. The condensation of oxidized coladonin (2) with various aryl aldehydes provided a series of new arylidene-based sesquiterpene coumarin derivatives (3a-m), which were characterized by NMR and ESI-HRMS experiments. All derivatives evaluated in vitro for their α-amylase inhibitory potential showed interesting α-amylase inhibition with IC50 values ranging from 7.24 to 28.98 μM. Notably, compounds 3k and 3m exhibited lower IC50 values (7.24 μM and 8.38 μM, respectively) compared to the standard (acarbose: IC50 = 9.83 μM). In addition, the structure-activity relationship (SAR) for all the compounds was studied. The most active compounds were found to be mixed-type inhibitors, which was revealed by kinetic studies. Furthermore, molecular in silico docking studies were established for all synthesized analogs with the binding site for the α-amylase enzyme.

Exploration of Anti-Diabetic Potential of Rubus ellipticus smith through Molecular Docking, Molecular Dynamics Simulation, and MMPBSA Calculation

Diabetes is a chronic metabolic disorder affecting a majority of the population worldwide. Hyperglycemia leading to diabetes mellitus could be managed through the inhibition of human pancreatic α-amylase enzyme. Phytochemicals are frequently reported to possess anti-diabetic activity through inhibition of normal functioning of α-amylase. This study aims to find potential α-amylase inhibitors from Rubus ellipticus Smith with molecular-level understanding using different computational tools. From the molecular docking calculations, rubuside F and rubuside D possessed good binding affinity of -10.0 kcal/mol and -9.9 kcal/mol, respectively better than the reference drugs (acarbose, miglitol, voglibose and metformin). Both the compounds showed good geometrical stability from molecular dynamics simulation accessed in terms of RMSD, hydrogen bond count, SASA, Rg and RMSF. Binding free energy changes of -27.92±4.15 kcal/mol and -28.75±4.15 kcal/mol, respectively for the two ligands indicated sustained thermodynamic spontaneity present in the adducts. The two phytochemicals could be proposed as potential inhibitors of human pancreatic α-amylase for the treatment of diabetes. Further, in vitro and in vivo experiments are recommended for the verification of computational insights in the course of drug design and discovery process.

Solvent-free synthesis, biological evaluation and in silico studies of novel 2-amino-7-(bis(2-hydroxyethyl)amino)-4H-chromene-3-carbonitrile derivatives as potential a-amylase inhibitors

Despite a wide range of kinase inhibitory activities exhibited by 2-amino-4H-chromenes, their potential application towards α-amylase inhibition remained rarely explored to date. For that purpose, a series of new 2-amino-7-(bis(2-hydroxyethyl)amino)-4(phenyl)-4H-chromene-3-carbonitrile derivatives has been synthesized via piperidine catalyzed solvent-free protocol and evaluated for their antidiabetic activity as potential α-amylase inhibitors. The dose-dependent in vitro α-amylase inhibition study revealed that, most of these compounds exhibited significant antidiabetic activity having more than 50 % α-amylase inhibition at the dose of 10 µg/mL. Among these, compound 5b was more potent than acarbose with 91 % inhibition of α-amylase and IC50 of 3.60 ± 0.01 µg/mL. Enzyme kinetic studies to estimate mode of inhibition showed that inhibition of α-amylase by compound 5b was competitive type with a Ki value of 0.97 µg/mL. Further, in silico studies of targeted compounds reinforced the results being involved in favorable binding interactions within the active site of α-amylase. Moreover, the in silico predicted properties of compound 5b regarded as a non-toxic and safer antidiabetic agent.

Phytochemical composition, anti-microbial, anti-oxidant and anti-diabetic effects of Solanum elaeagnifolium Cav. leaves: in vitro and in silico assessments

The aim of this study was to screen the chemical components of Solanum elaeagnifolium leaves and assess their therapeutic attributes with regard to their antioxidant, antibacterial, and antidiabetic activities. The antidiabetic effects were explored to determine the α-amylase and α-glucosidase inhibitory potential of the leaf extract. To identify the active antidiabetic drugs from the extracts, the GC-MS-screened molecules were docked with diabetes-related proteins using the glide module in the Schrodinger Tool. In addition, molecular dynamics (MD) simulations were performed for 100 ns to evaluate the binding stability of the docked complex using the Desmond module. The ethyl acetate had a significant total phenolic content (TPC), with a value of 79.04 ± 0.98 mg/g GAE. The ethanol extract was tested for its minimum inhibitory concentration (MIC) for its bacteriostatic properties. It suppressed the growth of B. subtilis, E. coli, P. vulgaris, R. equi and S. epidermis at a dosage of 118.75 µg/mL. Moreover, the IC50 values of the ethanol extract were determined to be 17.78 ± 2.38 in the α-amylase and and 27.90 ± 5.02 µg/mL in α-glucosidase. The in-silico investigation revealed that cyclolaudenol achieved docking scores of −7.94 kcal/mol for α-amylase. Likewise, the α-tocopherol achieved the docking scores of −7.41 kcal/mol for glycogen phosphorylase B and −7.21 kcal/mol for phosphorylase kinase. In the MD simulations, the cyclolaudenol and α-tocopherol complexes exhibited consistently stable affinities with diabetic proteins throughout the trajectory. Based on these findings, we conclude that this plant could be a good source for the development of novel antioxidant, antibacterial, and antidiabetic agents. Communicated by Ramaswamy H. Sarma

Docking Techniques for Unravelling the Molecular Mechanisms of Specioside of Kigelia africana Fruits

In this study, the inhibitors of α-amylase and aldose reductase, the key of proteins in diabetes mellitus, were isolated as compound speciosides from the Kigelia africana fruit Benth. Speciosides were selected as ligands for the receptors of α-amylase and aldose reductase in the molecular docking studies used by PyRx (0.8) for the inhibition of α-amylase and aldose reductase. The results showed that the α-amylase binding energy was 8.1 kcal/mol and aldose reductase was -9 kcal/mol. The ADME process showed that it was easily absorbed orally and distributed through the CNS, metabolized by CYP2D6, and excreted through renal Toxicity studies of speciosides showed no hepatotoxicity or skin sensitization. The in-silico studies of specioside compounds led to the development of potent α-amylase and aldose reductase inhibitors used to treat diabetic mellitus.

Inter- and intraspecific variability of phenolic content, antioxidant activities and α-amylase inhibitory potential of different bran and husk extracts from Algerian durum wheat (Triticum turgidum Desf.), barley (Hordeum vulgare L.) and their derived products (frik and mermez)

Inter- and intraspecific variability of phenolic content, antioxidant activities and α-amylase inhibitory potential of different bran and husk extracts from Algerian durum wheat (Triticum turgidum Desf.), barley (Hordeum vulgare L.) and their derived products (frik and mermez)

Exploring 1,3,4-Oxadiazole Derivatives as Potent α-Amylase Inhibitors: Design, Synthesis, and Biological Evaluation

Diabetes mellitus is a growing global health concern, and α-amylase inhibitors have been recognized as promising therapeutic agents for its treatment. This study aimed to design, synthesize and evaluate 1,3,4-oxadiazole derivatives as potential α-amylase inhibitors. A series of 1,3,4-oxadiazole derivatives were designed and subjected to in silico ADMET, Lipinski's Rule of Five, and drug-likeness analysis. The most promising compounds, SC2 and SC8, were synthesized and their α-amylase inhibitory activity was assessed in vitro. The interactions with the human α-amylase (PDB ID: 6Z8L) which is a target protein, was analyzed through molecular docking studies. The designed compounds complied with Lipinski's Rule of Five and exhibited favourable drug-likeness properties. In silico ADMET analysis predicted good absorption and distribution profiles. SC2 and SC8 demonstrated potent α-amylase inhibitory activity with IC50 values of 36.5±1.5 μg/mL and 45.2±2.1 μg/mL, respectively, compared to acarbose (68.9±3.2 μg/mL). Molecular docking revealed that both compounds formed crucial interactions with key amino acid residues in the enzyme’s active site. The binding affinities of SC2 and SC8 were -10.1 kcal/mol and -9.1 kcal/mol, respectively. The 1,3,4-oxadiazole derivatives, particularly SC2 and SC8, demonstrated potential as α-amylase inhibi- tors with favorable ADMET properties. These findings provide a basis for further optimization and development of these compounds as novel antidiabetic agents

Antioxidant, α-amylase and acetylcholinesterase inhibitory potential of Mazus pumilus (Japanese Mazus) extract: An in-vitro and in-silico study

Plant-derived secondary metabolites possess diverse biological activities that are beneficial to humans. Modern medications used for diabetes and Alzheimer’s often cause side effects, prompting reliance on traditional alternatives. Therefore, we aimed to uncover the potential of Mazus pumilus in countering diabetes and Alzheimer’s by in-vitro inhibition of α-amylase and AChE. Additionally, antioxidant activity and phytochemical analyses were performed. Mazus pumilusThe plant was extracted sequentially using n-hexane, ethyl acetate, dichloromethane, methanol, and water. The methanolic fraction, notably, manifested marked antioxidant efficacy against DPPH and ABTS radicals. Subsequently, this extract evinces noteworthy inhibitory attributes against α-amylase and AChE, respectively, in a competitive manner. Moreover, the bioactive phytoconstituents present in the methanolicextracts were determined through GC–MS analysis, and subsequent computational molecular docking studies revealed that these compounds strongly bound to the active site of both α-amylase and AChE. The calculated least binding energies, for α-amylase and AChE, underscore the viability of the molecular interactions. In conclusion, the antioxidant, antidiabetic, and anti-Alzheimer attributes of Mazus pumilus extract likely emanate from the synergistic interplay of its bioactive phytoconstituents. A comprehensive in-vitro and in-vivo study is essential to fully explore the anti-diabetic and anti-Alzheimer potential of secondary metabolites of Mazus pumilus.

Control of postprandial hyperglycemia by oral administration of the sea anemone mucus-derived α-amylase inhibitor (magnificamide)

Diabetes mellitus is a serious threat to human health in both developed and developing countries. Optimal disease control requires the use of a diet and a combination of several medications, including oral hypoglycemic agents such as α-glucosidase inhibitors. Currently, the arsenal of available drugs is insufficient, which determines the relevance of studying new potent α-amylase inhibitors. We implemented the recombinant production of sea anemone derived α-amylase inhibitor magnificamide in Escherichia coli. Peptide was isolated by a combination of liquid chromatography techniques. Its folding and molecular weight was proved by 1H NMR and mass spectrometry. The Ki value of magnificamide against human pancreatic α-amylase is 3.1 nM according to Morrison equation for tight binding inhibitors. Our study of the thermodynamic characteristics of binding of magnificamide to human salivary and pancreatic α-amylases by isothermal titration calorimetry showed the presence of different binding mechanisms with Kd equal to 0.11 µM and 0.1 nM, respectively. Experiments in mice with streptozotocin-induced diabetes mimicking diabetes mellitus type 1 were used to study the efficiency of magnificamide against postprandial hyperglycemia. It was found that at a dose of 0.005 mg kg–1, magnificamide effectively blocks starch breakdown and prevents the development of postprandial hyperglycemia in T1D mice. Our results demonstrated the therapeutic potential of magnificamide for the control of postprandial hyperglycemia.

A Comparative Analysis of Radical Scavenging, Antifungal and Enzyme Inhibition Activity of 3'-8″-Biflavones and Their Monomeric Subunits.

Biflavonoids are dimeric forms of flavonoids that have recently gained importance as an effective new scaffold for drug discovery. In particular, 3'-8″-biflavones exhibit antiviral and antimicrobial activity and are promising molecules for the treatment of neurodegenerative and metabolic diseases as well as cancer therapies. In the present study, we directly compared 3'-8″-biflavones (amentoflavone, bilobetin, ginkgetin, isoginkgetin, and sciadopitysin) and their monomeric subunits (apigenin, genkwanin, and acacetin) and evaluated their radical scavenging activity (with DPPH), antifungal activity against mycotoxigenic fungi (Alternaria alternata, Aspergillus flavus, Aspergillus ochraceus, Fusarium graminearum, and Fusarium verticillioides), and inhibitory activity on enzymes (acetylcholinesterase, tyrosinase, α-amylase, and α-glucosidase). All the tested compounds showed weak radical scavenging activity, while antifungal activity strongly depended on the tested concentration and fungal species. Biflavonoids, especially ginkgetin and isoginkgetin, proved to be potent acetylcholinesterase inhibitors, whereas monomeric flavonoids showed higher tyrosinase inhibitory activity than the tested 3'-8″-biflavones. Amentoflavone proved to be a potent α-amylase and α-glucosidase inhibitor, and in general, 3'-8″-biflavones showed a stronger inhibitory potential on these enzymes than their monomeric subunits. Thus, we can conclude that 3'-8″-dimerization enhanced acetylcholinesterase, α-amylase, and α-glucosidase activities, but the activity also depends on the number of hydroxyl and methoxy groups in the structure of the compound.

Synthesis, in vitro α-glucosidase, α-amylase inhibitory potentials and molecular docking study of benzimidazole bearing sulfonamide analogues

Synthesis, in vitro α-glucosidase, α-amylase inhibitory potentials and molecular docking study of benzimidazole bearing sulfonamide analogues